Aortic Calcification Is Associated With Aortic Stiffness and Isolated Systolic Hypertension in Healthy Individuals

Chang

et al. 2016

JAHA

BackgroundThe structure of the aorta is considered to influence exercise systolic blood pressure (SBP) response, which, in turn, might impact upon adverse outcomes. The current study sought to investigate the relationship of aortic calcification and exercise SBP with adverse outcomes among elderly individuals.Methods and ResultsWe retrospectively reviewed 702 elderly individuals (>65 years of age) without obstructive coronary artery disease (CAD; luminal stenosis <50%) who underwent coronary computed tomography (CT) and exercise treadmill testing. ΔSBP stage2 and ΔSBP peak were defined as the difference in systolic blood pressure (SBP) between rest and stage 2 or peak exercise, respectively. Thoracic aortic calcium score (TACS) and coronary artery calcium score (CACS) were measured using CT scanning procedures. The primary endpoints were defined as all‐cause death, admission for heart failure, obstructive CAD requiring coronary intervention, and stroke. In multivariable models, ΔSBP stage2 and ΔSBP peak were positively related with log(TACS+1), even after adjusting for various clinical variables, baseline SBP, and CACS (P<0.001). During a median follow‐up period of 65 months, there were 59 events (8.4%). In a multivariate Cox regression model, independent predictors for all events were age (hazard ratio [HR], 1.12; 95% CI, 1.05–1.19; P<0.001), dyslipidemia (HR, 1.96; 95% CI, 1.14–3.37; P=0.015), and the 4th quartile of TACS (HR, 1.24; 95% CI, 1.03–1.49; P=0.024). Among individual events, the 4th quartile of TACS was the only independent predictor for stroke (HR, 2.15; 95% CI, 1.09–5.13; P=0.044), whereas CACS ≥400 mm3 was an independent predictor for obstructive CAD requiring intervention (HR, 7.04; 95% CI, 1.58–31.36; P=0.010).ConclusionsAortic calcification was related to SBP response during exercise and was an independent predictor for outcomes, especially stroke, regardless of resting SBP or CACS.

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Association of Thoracic Aorta Calcium Score With Exercise Blood Pressure Response and Clinical Outcomes in Elderly Individuals: Differential Impact of Aorta Calcification Compared With Coronary Artery Calcification

Chang

et al. 2016

JAHA

“…5,18 Taken together, these data support the notion that patients with stiffer arteries might be less responsive to traditional antihypertensive drug therapy. Indeed, we have demonstrated recently that patients with ISH have increased aortic calcification compared with agematched normotensive individuals, 19 suggesting a need for novel "destiffening" therapies in patients with ISH.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Effects of Antihypertensive Agents on Central Blood Pressure and Arterial Stiffness in Isolated Systolic Hypertension

et al. 2009

Self Cite

Abstract-Isolated systolic hypertension is an important risk factor for cardiovascular disease and results primarily from elastic artery stiffening. Although various drug therapies are used to lower peripheral blood pressure (BP) in patients with isolated systolic hypertension, the effects of the 4 major classes of antihypertensive agents on central BP, pulse pressure (PP) amplification, and arterial stiffness in this condition are not clear. Fifty-nine patients over the age of 60 years with untreated isolated systolic hypertension (systolic BP Ն140 mm Hg and diastolic BP Յ90 mm Hg) were randomly assigned to receive 1 of the following 4 antihypertensive agents: perindopril, atenolol, lercanidipine, or bendrofluazide. BP was measured using a mercury sphygmomanometer, and augmentation index and carotid-femoral (aortic) pulse wave velocity were measured at baseline, after 2 weeks of placebo therapy, and at the end of 10 weeks of active therapy. Peripheral systolic BP and peripheral PP were reduced similarly after treatment with all 4 classes of drug. However, central PP was only reduced significantly by perindopril, lercanidipine, and bendrofluazide, whereas atenolol had no effect. Lercanidipine reduced the augmentation index, whereas atenolol increased it. Aortic pulse wave velocity was not changed by any of the drugs. In summary, despite similar reductions in peripheral systolic and PPs with the 4 classes of drug, changes in central pressure and augmentation index varied. Because central PP and increased wave reflections are considered important risk factors in patients with isolated systolic hypertension, the choice of therapy may be influenced by these findings in the future. Key Words: antihypertensive therapy Ⅲ central pressure Ⅲ pulse pressure amplification Ⅲ pulse wave velocity Ⅲ isolated systolic hypertension I solated systolic hypertension (ISH) is a common condition in older individuals and is characterized by increased arterial stiffness 1 and an elevated risk of cardiovascular events. Several of the main antihypertensive drug classes are effective in lowering brachial blood pressure (BP) in patients with ISH. 2,3 However, the Losartan Intervention for Endpoint Reduction in Hypertension Study showed that, despite similar reductions in brachial BP, patients randomly assigned to initial therapy with losartan had a better outcome than those randomly assigned to atenolol (with subsequent add-in therapy using hydrochlorothiazide for both study arms) and that this effect was more pronounced in older patients with systolic hypertension. 4 The Preterax in Regression of Arterial Stiffness in a Controlled Double-Blind Study reported previously that different antihypertensive drugs exert differential effects on brachial versus aortic pressure, 5 and a growing body of evidence now supports these findings 6 -8 and provides a potential explanation for the results of the Losartan Intervention for Endpoint Reduction in Hypertension Study. Indeed, more recently, the Conduit Artery Function Evaluation Study 9 showed that...

“…Vascular calcification is a process thought to be driven by inflammation. Animal models of arterial calcification result in a marked increase in stiffening and calcification is thought to cause arterial stiffening in chronic kidney disease, and McEniery et al 7 have previously demonstrated a relation between arterial calcification and stiffening in the general population. A distinction is often made between diffuse medial calcification occurring in diabetes mellitus and chronic kidney disease and focal calcification localized to atherosclerotic plaque, but these 2 conditions may represent extremes of a continuum.…”

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confidence: 99%

Arterial Stiffening

Cecelja

Chowienczyk

2010

Hypertension

A ortic and large artery stiffening, hallmarks of vascular aging, 1 are predictive of cardiovascular events, particularly in subjects with hypertension and components of the metabolic syndrome. 2,3 One hypothesis is that stiffening is a consequence of the combined insult of risk factors on the vascular wall. 3 However, cross-sectional studies show little association of arterial stiffness with conventional risk factors other than blood pressure. 4 The interrelationship of arterial stiffness with blood pressure makes it fascinating for the hypertensionologist. An elevation in mean arterial pressure stretches the arterial wall, leading to a functional increase in stiffness. Stiffening associated with a chronic elevation of blood pressure (ie, hypertension) may be because of distention of the arterial wall but could also be explained by structural changes of the arterial wall. The degree to which the latter explains hypertension-associated stiffening is still disputed. 5 Finally, the effect of increased stiffening is to increase pulse pressure and systolic blood pressure. Disentangling these interrelationships is challenging, and the causal link between blood pressure and arterial stiffness has not been elucidated. Longitudinal studies that provide insight into the role of blood pressure and novel risk factors on arterial stiffening are, thus, particularly useful.In this issue of Hypertension, McEniery et al 6 present an analysis of prospective risk factors for aortic stiffness in men from the Caerphilly Prospective Study. In a cohort of 825 men of mean age 74 years, aortic pulse wave velocity (PWV), regarded by many as the gold-standard measure of arterial stiffness, was measured during the most recent follow-up phase of the Caerphilly Prospective Study. The relationship of PWV to blood pressure and risk factors at the time of its measurement and over an average follow-up of 20 years was examined. PWV (adjusted for "current risk factors") was closely correlated with the pulse pressureϫheart rate product over the 20-year follow-up. There was also a highly significant correlation of PWV with baseline and subsequent measures of C-reactive protein. Aside from weak correlations with blood glucose, triglycerides, and waist diameter, PWV was not correlated with any other risk factor. A limitation of the study, which the authors were keen to point out, is that they did not have longitudinal measures of PWV. Thus the association of PWV with longitudinal measures of pulse pressure could be explained by pulse pressure acting as a surrogate for PWV. Similarly, the contribution of heart rate could be explained in part by the functional increase in PWV that accompanies an acute elevation in heart rate and that is probably attributable to visco-elastic properties of the arterial wall. Nonetheless, the finding of a relationship between PWV and repetitive cyclic stress is appealing, because such stress is thought to result in stress fracturing of elastin and consequent stiffening.