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Showing papers by "Joseph L. Izzo published in 2008"


Journal ArticleDOI
TL;DR: Among individuals with systolic hypertension, increased PP is primarily attributable to increased wall stiffness and reduced aortic diameter rather than premature wave reflection, and an inverse relation between PP and aorti diameter remained significant.
Abstract: Systolic hypertension is associated with increased pulse pressure (PP) and increased risk for adverse cardiovascular outcomes. However the pathogenesis of increased PP remains controversial. One hypothesis suggests that aortic dilatation, wall stiffening and increased pulse wave velocity result from elastin fragmentation, leading to a premature reflected pressure wave that contributes to elevated PP. An alternative hypothesis suggests that increased proximal aortic stiffness and reduced aortic diameter leads to mismatch between pressure and flow, giving rise to an increased forward pressure wave and increased PP. To evaluate these two hypotheses, we measured pulsatile hemodynamics and proximal aortic diameter directly using tonometry, ultrasound imaging, and Doppler in 167 individuals with systolic hypertension. Antihypertensive medications were withdrawn for at least 1 week before study. Patients with PP above the median (75 mm Hg) had lower aortic diameter (2.94+/-0.36 versus 3.13+/-0.28 cm, P<0.001) and higher aortic wall stiffness (elastance-wall stiffness product: 16.1+/-0.7 versus 15.7+/-0.7 ln[dyne/cm], P<0.001) with no difference in augmentation index (19.9+/-10.4 versus 17.5+/-10.0%, P=0.12). Aortic diameter and wall stiffness both increased with advancing age (P<0.001). However, an inverse relation between PP and aortic diameter remained significant (P<0.001) in models that adjusted for age, sex, height, and weight and then further adjusted for aortic wall stiffness, augmentation index, and mean arterial pressure. Among individuals with systolic hypertension, increased PP is primarily attributable to increased wall stiffness and reduced aortic diameter rather than premature wave reflection.

167 citations


Journal ArticleDOI
TL;DR: Support for the BP‐lowering benefits of complementary antihypertensive therapy with amlodipine and valsartan in patients with hypertension uncontrolled by previous monotherapy is provided.
Abstract: In this randomized, double-blind, multicenter study, patients whose blood pressure (BP) was uncontrolled by monotherapy were switched directly to amlodipine/valsartan 5/160 mg (n=443) or 10/160 mg (n=451). After 16 weeks, BP control (levels <140/90 mm Hg or <130/80 mm Hg for diabetics) was achieved in 72.7% (95% confidence interval [CI], 68.6-76.9) of patients receiving amlodipine/valsartan 5/160 mg and in 74.8% (95% CI, 70.8-78.9) receiving amlodipine/valsartan 10/160 mg. Incremental reductions from baseline in mean sitting systolic and diastolic BP were significantly greater with the higher dose (20.0+/-0.7 vs 17.5+/-0.7 mm Hg; P=.0003 and 11.6+/-0.4 vs 10.4+/-0.4 mm Hg; P=.0046). Incremental BP reductions were also achieved with both regimens irrespective of previous monotherapy, hypertension severity, diabetic status, body mass index, and age. Peripheral edema was the most frequent adverse event. These results provide support for the BP-lowering benefits of complementary antihypertensive therapy with amlodipine and valsartan in patients with hypertension uncontrolled by previous monotherapy.

113 citations


Journal Article
TL;DR: In this paper, the authors measured pulsatile hemodynamics and proximal aortic diameter directly using tonometry, ultrasound imaging, and Doppler in 167 individuals with systolic hypertension.
Abstract: -Systolic hypertension is associated with increased pulse pressure (PP) and increased risk for adverse cardiovascular outcomes. However the pathogenesis of increased PP remains controversial. One hypothesis suggests that aortic dilatation, wall stiffening and increased pulse wave velocity result from elastin fragmentation, leading to a premature reflected pressure wave that contributes to elevated PP. An alternative hypothesis suggests that increased proximal aortic stiffness and reduced aortic diameter leads to mismatch between pressure and flow, giving rise to an increased forward pressure wave and increased PP. To evaluate these two hypotheses, we measured pulsatile hemodynamics and proximal aortic diameter directly using tonometry, ultrasound imaging, and Doppler in 167 individuals with systolic hypertension. Antihypertensive medications were withdrawn for at least 1 week before study. Patients with PP above the median (75 mm Hg) had lower aortic diameter (2.94±0.36 versus 3.13±0.28 cm, P<0.001) and higher aortic wall stiffness (elastance-wall stiffness product: 16.1±0.7 versus 15.7±0.7 1n[dyne/cm], P<0.001) with no difference in augmentation index (19.9 ±10.4 versus 17.5± 10.0%, P=0.12). Aortic diameter and wall stiffness both increased with advancing age (P<0.001). However, an inverse relation between PP and aortic diameter remained significant (P<0.001) in models that adjusted for age, sex, height, and weight and then further adjusted for aortic wall stiffness, augmentation index, and mean arterial pressure. Among individuals with systolic hypertension, increased PP is primarily attributable to increased wall stiffness and reduced aortic diameter rather than premature wave reflection.

14 citations


Journal ArticleDOI
TL;DR: Clinically, the most prevalent forms of hypertension, isolated systolic and white-coat hypertension, are poorly responsive to agents that easily lower diastolic blood pressure, which leads directly to the inability of the us food and Drug administration to approve these agents as antihypertensives, which by convention must lower both syStolic and diastolics blood pressure.
Abstract: Vol. 10 no. 3 MarCH 2008 174 Many individuals in the hypertension community have historically failed to recognize the many different pathogenetic origins and phenotypic expressions of the hypertension syndrome. Why is recognition and acceptance of this heterogeneity so important now? Despite the fact that hypertension is the single most important risk factor for cardiovascular disease, in large measure, the field is stagnant. unless we agree on a scientifically accurate, clinically meaningful classification system for hypertension, the rate of basic discovery will slow even further, and improvements in clinical management will lag. Those who think that this is just melodrama should simply look at the number of new investigators coming into the field, the numbers of new drugs under development, and the diminishing rate of improvement in cardiovascular disease. Clinically, the most prevalent forms of hypertension, isolated systolic and white-coat hypertension, are poorly responsive to agents that easily lower diastolic blood pressure. Does this pattern signify that isolated diastolic, isolated systolic, and reactive forms of hypertension arise from fundamentally different mechanisms? at present, our antihypertensive drug armamentarium largely consists of arteriolar dilators. shouldn’t we also be working on approaches to reduce vasoreactivity and central arterial stiffness? agents such as collagen cross-link breakers actually lower systolic but raise diastolic blood pressure. Here, our failure to recognize systolic hypertension as distinct from diastolic hypertension leads directly to the inability of the us food and Drug administration to approve these agents as antihypertensives, which by convention must lower both systolic and diastolic blood pressure. reliable solutions to most of the important therapeutic dilemmas in hypertension would be facilitated by applying our knowledge of the diverse mechanisms that underlie the particular hypertension phenotype. Would anyone argue that the subtyping of diabetes into insulin insufficiency and insulin resistance has provided marked improvements in therapy based on improved understanding of pathophysiology? from a translational research perspective, there are many different animal models of hypertension, each with a unique natural history and phenotypic expression. no single animal model describes all aspects of human hypertension; their only common feature is the chronic elevation of mean arterial pressure. in humans, aside from some rare monogenetic forms of hypertension, there does not seem to be a strong genetic fingerprint. Does it therefore follow that hypertension is an acquired characteristic? or could the contribution of several major genetic components have been confounded by our failure to subtype the syndrome into relevant “intermediate phenotypes” or “endophenotypes”? if wide pulse pressure hypertension is related predominantly to increased aortic impedance, or if white-coat hypertension is related to altered neural control, why should either condition be closely related to a gene that controls arteriolar structure or function? in fairness, we have made some meaningful advances in shifting the paradigm in hypertension. isolated systolic hypertension, which accounts for more than half of all hypertension cases, is now recognized worldwide as a greater public health www.lejacq.com ID: 8083 E d i t o r i a l

3 citations


Journal ArticleDOI
TL;DR: It is concluded that contributions of smaller diameter and increased wave reflection to increased pulse pressure may not be mutually exclusive and add that only properly conducted, longitudinal studies, not the analysis of an arbitrarily subdivided cross-sectional study, can inform a definite conclusion.
Abstract: We thank Richart et al1 and Roman and Devereux2 for their careful reading of our article3 and thoughtful feedback. Richart et al1 raise 3 points, described below. First, dichotomization of the sample at the overall median pulse pressure led to overrepresentation of women, who are shorter, in the high pulse pressure group. Wave reflection may have contributed substantially to higher pulse pressure in these shorter individuals. Second, in our Figure 3, women and men are pooled without any evidence that the slopes of the regression lines are the same in men and women. Third, peak wall tension seems to be higher in the proximal aorta in the high pulse pressure group and may have contributed to premature mechanical wear and consequent wall stiffening. They conclude that contributions of smaller diameter and increased wave reflection to increased pulse pressure may not be mutually exclusive and add that only properly conducted, longitudinal studies, not the analysis of an arbitrarily subdivided cross-sectional study, can inform a definite conclusion. Regarding dichotomization of the sample at the median pulse pressure, we wish to point out that the primary pulse pressure model, presented in our Table 3 and Figure 3, considered pulse pressure as a continuous variable. Furthermore, as noted in the article, the models …

1 citations