Abstract-Pulse pressure varies throughout the arterial tree, resulting in a gradient between central and peripheral pressure.Factors such as age, heart rate, and height influence this gradient. However, the relative impact of cardiovascular risk factors and atheromatous disease on central pressure and the normal variation in central pressure in healthy individuals are unclear. Seated peripheral (brachial) and central (aortic) blood pressures were assessed, and the ratio between aortic and brachial pulse pressure (pulse pressure ratio, ie, 1/amplification) was calculated in healthy individuals, diabetic subjects, patients with cardiovascular disease, and in individuals with only 1 of the following: hypertension, hypercholesterolemia, or smoking. The age range was 18 to 101 years, and data from 10 613 individuals were analyzed. Compared with healthy individuals, pulse pressure ratio was significantly increased (ie, central systolic pressure was relatively higher) in individuals with risk factors or disease (PϽ0.01 for all of the comparisons). Although aging was associated with an increased pulse pressure ratio, there was still an averageϮSD difference between brachial and aortic systolic pressure of 11Ϯ4 and 8Ϯ3 mm Hg for men and women aged Ͼ80 years, respectively. Finally, stratifying individuals by brachial pressure revealed considerable overlap in aortic pressure, such that Ͼ70% of individuals with high-normal brachial pressure had similar aortic pressures as those with stage 1 hypertension. These data demonstrate that cardiovascular risk factors affect the pulse pressure ratio, and that central pressure cannot be reliably inferred from peripheral pressure. However, assessment of central pressure may improve the identification and management of patients with elevated cardiovascular risk. Key Words: central pressure Ⅲ brachial pressure Ⅲ pulse pressure ratio Ⅲ pulse pressure amplification Ⅲ hypertension Ⅲ cardiovascular risk factors T he value of brachial artery pressure as a predictor of future cardiovascular disease is firmly established. 1 Recently, greater emphasis has been placed on pulse pressure (PP), a surrogate of large artery stiffness, especially in older individuals. 2,3 However, there is a gradual widening of PP moving from the central to the peripheral arteries, 4 mainly because of a rise in systolic pressure. Moreover, emerging data suggest that central PP may be more closely correlated with surrogate measures of cardiovascular risk, such as left ventricular mass 5 and carotid intima-media thickness, 6 than brachial PP. Furthermore, central PP appears to be an independent predictor of future cardiovascular risk in selected patient groups, 7,8 although whether it outperforms brachial PP more generally remains to be confirmed. The Conduit Artery Function Evaluation Study 9 further highlighted the potential importance of central pressure by confirming that antihypertensive drugs can have differential effects on central and peripheral PP, which translate into differences in outcome.The disparity betwe...

Background-Arterial stiffness is an independent determinant of cardiovascular risk, and arterial stiffening is the predominant abnormality in systolic hypertension. Elastin is the main elastic component of the arterial wall and can be degraded by a number of enzymes, including matrix metalloproteinase-9 (MMP-9) and MMP-2. We hypothesized that elastase activity would be related to arterial stiffness and tested this using isolated systolic hypertension (ISH) as a model of stiffening and separately in a large cohort of healthy individuals. Methods and Results-A total of 116 subjects with ISH and 114 matched controls, as well as 447 individuals free from cardiovascular disease were studied. Aortic and brachial pulse wave velocity (PWV) and augmentation index were determined. Blood pressure, lipids, C-reactive protein, MMP-9, MMP-2, serum elastase activity (SEA), and tissue-specific inhibitor 2 of metalloproteinases were measured. Aortic and brachial PWV, MMP-9, MMP-2, and SEA levels were increased in ISH subjects compared with controls (Pϭ0.001). MMP-9 levels correlated linearly and significantly with aortic (rϭ0.45; Pϭ0.001) and brachial PWV (rϭ0.22; Pϭ0.002), even after adjustments for confounding variables. In the younger, healthy subjects, MMP-9 and SEA were also independently associated with aortic PWV. Conclusions-Aortic stiffness is related to MMP-9 levels and SEA, not only in ISH, but also in younger, apparently healthy individuals. This suggests that elastases including MMP-9 may be involved in the process of arterial stiffening and development of ISH.

Background— Rheumatoid arthritis (RA) is associated with increased cardiovascular risk, which is not explained by traditional cardiovascular risk factors but may be due in part to increased aortic stiffness, an independent predictor of cardiovascular mortality. In the present study, our aim was to establish whether aortic stiffness is increased in RA and to investigate the relationship between inflammation and aortic stiffness. In addition, we tested the hypothesis that aortic stiffness could be reduced with anti–tumor necrosis factor-α (TNF-α) therapy. Methods and Results— Aortic pulse-wave velocity (PWV), augmentation index, and blood pressure were measured in 77 patients with RA and in 142 healthy individuals. Both acute and chronic inflammatory measures and disease activity were determined. The effect of anti-TNF-α therapy on PWV and endothelial function was measured in 9 RA patients at 0, 4, and 12 weeks. Median (interquartile range) aortic PWV was significantly higher in subjects with RA than in control subjects (8.35 [7.14 to 10.24] versus 7.52 [6.56 to 9.18] m/s, respectively; P =0.005). In multiple regression analyses, aortic PWV correlated independently with age, mean arterial pressure, and log-transformed C-reactive protein ( R 2 =0.701; P <0.0001). Aortic PWV was reduced significantly by anti-TNF-α therapy (8.82±2.04 versus 7.94±1.86 versus 7.68±1.56 m/s at weeks 0, 4, and 12, respectively; P <0.001); concomitantly, endothelial function improved. Conclusions— RA is associated with increased aortic stiffness, which correlates with current but not historical measures of inflammation, suggesting that increased aortic stiffness may be reversible. Indeed, anti-TNF-α therapy reduced aortic stiffness to a level comparable to that of healthy individuals. Therefore, effective control of inflammation may be of benefit in reducing cardiovascular risk in patients with RA.

Abstract-Arterial stiffness is an independent predictor of mortality and is regulated by a number of factors, including vascular smooth muscle tone. However, the relationship between endothelial function and definitive measures of arterial stiffness and wave reflections has not been described in healthy individuals. Therefore, we tested the hypothesis that endothelial function is inversely correlated with aortic pulse wave velocity (PWV), central pulse pressure, and augmentation index in healthy individuals. Peripheral and central pulse pressure and augmentation index were determined at rest, and global endothelial function was measured using pulse wave analysis and administration of sublingual nitroglycerin and inhaled albuterol. Aortic PWV was also determined at baseline in a subset of 89 subjects.In a separate group of subjects (nϭ89), aortic PWV was measured and brachial artery flow-mediated dilatation assessed as a measure of conduit artery endothelial function. Key Words: nitric oxide Ⅲ endothelium-derived factors Ⅲ blood pressure Ⅲ pulse Ⅲ arteries E ndothelial dysfunction, characterized by a reduced bioavailability of endothelium-derived NO, is an important step in the progression of atherosclerosis. Indeed, resistance vessel, 1 conduit artery, 2 and coronary 3,4 endothelial dysfunction independently predict all-cause and cardiovascular mortality. A number of risk factors for cardiovascular disease, including age, 5 hypertension, 1 obesity, 6 hypercholesterolemia, 7 diabetes, 8 and smoking, 9 are associated with systemic endothelial dysfunction. Interestingly, these risk factors are also associated with increased elastic artery stiffness, 10,11 which is itself an important predictor of outcome in a number of patient groups. [12][13][14][15] Removal of the vascular endothelium alters arterial stiffness in animal models, 16 and we have demonstrated recently that blocking NO synthesis increases local arterial stiffness, 17,18 suggesting that endotheliumderived NO contributes to the regulation of large artery stiffness in vivo.Support for this hypothesis stems from the observation that brachial artery pulse pressure, a surrogate measure of large artery stiffness, correlates with coronary 19 and resistance vessel 20 endothelial function in hypertensive patients and controls. However, direct evidence of a relationship between endothelial function and more definitive measures of arterial stiffness is largely limited to studies in patients with cardiovascular disease and risk factors, [21][22][23][24][25][26] and the relationship between endothelial function and aortic (carotid-femoral) pulse wave velocity (PWV), the current "gold-standard" measure of stiffness, in healthy normotensive individuals, who are free of the potentially confounding influence of cardiovascular disease, has not been well-described. Moreover, as we 27 and others 28 have shown previously, brachial pulse pressure does not always provide an accurate indication of central pulse pressure, and the relationship between endothelial function and c...

Abstract-Isolated systolic hypertension is a common condition in individuals aged older than 60 years. However, isolated systolic hypertension has also been described in young individuals, although the mechanisms are poorly understood. We hypothesized that in young adults, isolated systolic hypertension and essential hypertension have different hemodynamic mechanisms and the aim of this study was to test this hypothesis in a cohort of subjects from The ENIGMA Study. Peripheral and central blood pressure, aortic pulse wave velocity, cardiac output, stroke volume, and peripheral vascular resistance were determined in 1008 subjects, aged 17 to 27 years. Compared with normotensive subjects, those with isolated systolic hypertension had significantly higher peripheral, central, and mean blood pressure, aortic pulse wave velocity, cardiac output, and stroke volume (PϽ0.001 for all comparisons). However, there were no differences in pulse pressure amplification, heart rate, or peripheral vascular resistance between the two groups. Compared with subjects with essential hypertension, mean pressure, heart rate, and peripheral vascular resistance were all significantly lower in isolated systolic hypertensive subjects, but pulse pressure amplification, aortic pulse wave velocity, cardiac output, and stroke volume were higher (PϽ0.001 for all comparisons). We have demonstrated that in young adults, isolated systolic hypertension and essential hypertension arise from different hemodynamic mechanisms. Isolated systolic hypertension appears to result from an increased stroke volume and/or aortic stiffness, whereas the major hemodynamic abnormality underlying essential hypertension is an increased peripheral vascular resistance. Long-term follow-up of these individuals is now required to determine whether they are at increased risk compared with age-matched normotensive individuals. Key Words: arterial stiffness Ⅲ hemodynamics Ⅲ isolated systolic hypertension Ⅲ stroke volume Ⅲ young adults H ypertension is a common disorder, affecting Ϸ25% of the overall population 1,2 and is a major risk factor for cardiovascular disease. Epidemiological data 2,3 not only show an age-related change in the incidence of hypertension but also in its form. In those aged younger than 50, the predominant form of hypertension is essential hypertension (EH), involving elevation of systolic (SBP) and diastolic pressure (DBP), or DBP alone, which is characterized by increased peripheral vascular resistance (PVR). However, in older individuals, the most common form of hypertension is isolated systolic hypertension (ISH). This affects Ϸ50% of those aged older than 60 4 and, in contrast to EH, is thought to be caused mainly by large artery stiffening, resulting from disruption and fatigue-fracture of elastic fibers. Therefore, ISH is often considered to be an exaggeration of "normal" age-related stiffening seen in most populations. Indeed, we 5 and others 6 have shown that aortic pulse wave velocity (PWV), a measure of arterial stiffness, is increased in pa...

No abstract

Maximum FMD percentage change from baseline is the most reproducible of the response curve measures and best identifies those with risk factors. Flow-mediated dilation measured by B-ED is robust and practical to assess the effect of interventions on endothelial function in clinical trials.

Objective-C-reactive protein (CRP) levels predict outcome in healthy individuals and patients with atherosclerosis.Arterial stiffness also independently predicts all-cause and cardiovascular mortality and may be involved in the process of atherosclerosis. The aim of this study was to investigate the relationship between stiffness and inflammation in a cohort of healthy individuals. Methods and Results-Pulse wave velocity (PWV) and blood pressure were assessed in 427 individuals. Subjects with cardiovascular disease, diabetes, hypercholesterolemia and those using medication were excluded. CRP correlated with age, mean arterial pressure (MAP), brachial and aortic PWV, and pulse pressures. In multiple regression models, aortic PWV correlated independently with age, CRP, male gender, and MAP (R 2 ϭ0.593; PϽ0.001). CRP was also independently associated with brachial PWV. Aortic augmentation index correlated with age, gender, MAP, and inversely with heart rate and height, but not with CRP (R 2 ϭ0.794; PϽ0.001). Aortic, carotid, and brachial pulse pressures were also independently associated with CRP levels. Conclusion-Aortic and brachial PWV, and pulse pressure, relate to levels of inflammation in healthy individuals, suggesting that inflammation may be involved in arterial stiffening. Anti-inflammatory strategies may, therefore, be of benefit in reducing arterial stiffness and thus cardiovascular risk, especially in patients with premature arterial stiffening. Key Words: C-reactive protein Ⅲ pulse wave analysis Ⅲ augmentation index Ⅲ pulse wave velocity Ⅲ inflammation T he pathogenesis of atherosclerosis remains incompletely understood, but inflammation is thought to play an important role. 1 Several studies have demonstrated that serum levels of the acute phase protein, C-reactive protein (CRP), independently predict outcome in patients with cardiovascular disease 2,3 and in apparently healthy individuals. 4,5 Levels of CRP also correlate with endothelial function, an independent predictor of cardiovascular risk, 6 in patients with coronary artery disease. 7 Moreover, CRP has direct proinflammatory effects on human endothelial cells in vitro 8 and can induce endothelial dysfunction. 9 Aortic pulse wave velocity (PWV), a measure of aortic distensibility, predicts mortality in patients with end-stage renal failure, hypertension, diabetes, and older otherwise healthy individuals, independently of known confounding factors. 10 -13 Interestingly, recent evidence suggests that brachial pulse pressure, a surrogate measure of arterial stiffness, is correlated with CRP and interleukin-6 (IL-6) levels in apparently healthy men. 14,15 Moreover, an association between CRP and aortic PWV has been reported in subjects with end-stage renal failure. 16 However, whether there is any relationship between inflammation and central pulse pressure or more direct indices of arterial stiffness such as aortic PWV in healthy individuals is unclear. We hypothesized that CRP levels would be correlated with aortic PWV and central pulse pressure...