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Clustering of arterial blood pressure (BP) waveform parameters could summarize complex information into distinct elements, which could be used to investigate cumulative (nonredundant) associations. We investigated this hypothesis in a large, adult population-based study (ViDA trial [Vitamin D Assessment] trial). To interpret the clusters and evaluate their usefulness, we examined their predictors and associations with cardiovascular events. In 4253 adults (mean age 65 years; 55% male) without a prior cardiovascular event, suprasystolic oscillometry was performed, yielding aortic pressure waveforms and several hemodynamic parameters. Participants were followed up for 4.6 years (median), accruing 300 cardiovascular events. Principal component analysis reduced 14 arterial waveform parameters to 3 uncorrelated factors that together explained 90% of the variability of the original data. Factors 1, 2, and 3 appeared to represent BP pulsatility, mean BP, and wave reflection, respectively. Across 6 antihypertensive drug classes, there were no differences in brachial systolic ( P =0.23) and diastolic ( P =0.13) BP; but there were significant variations in factor 3 ( P <0.0001), especially for β-blocker use. The first and third factors were positively associated with cardiovascular events (multivariable-adjusted standardized hazard ratio [95% CI]=1.33 [1.18-1.50] and 1.15 [1.02-1.30], respectively), whereas the second factor had a J-shaped relationship, with a nadir corresponding to a brachial diastolic BP of ≈75 mm Hg. In conclusion, BP pulsatility, mean BP, and wave reflection are prognostically meaningful, distinct aspects of arterial function that can be used to summarize physiological variations in multiple arterial waveform parameters and identify truly cumulative associations when used as cardiovascular risk outcomes.

Background: The effects of monthly, high-dose, long-term (≥1-year) vitamin D supplementation on central blood pressure (BP) parameters are unknown., Methods and Results: A total of 517 adults (58% male, aged 50-84 years) were recruited into a double-blinded, placebo-controlled trial substudy and randomized to receive, for 1.1 years (median; range: 0.9-1.5 years), either (1) vitamin D 3 200 000 IU (initial dose) followed 1 month later by monthly 100 000-IU doses (n=256) or (2) placebo monthly (n=261). At baseline (n=517) and follow-up (n=380), suprasystolic oscillometry was undertaken, yielding aortic BP waveforms and hemodynamic parameters. Mean deseasonalized 25-hydroxyvitamin D increased from 66 nmol/L (SD: 24) at baseline to 122 nmol/L (SD: 42) at follow-up in the vitamin D group, with no change in the placebo group. Despite small, nonsignificant changes in hemodynamic parameters in the total sample (primary outcome), we observed consistently favorable changes among the 150 participants with vitamin D deficiency (<50 nmol/L) at baseline. In this subgroup, mean changes in the vitamin D group (n=71) versus placebo group (n=79) were -5.3 mm Hg (95% confidence interval [CI], -11.8 to 1.3) for brachial systolic BP ( P =0.11), -2.8 mm Hg (95% CI, -6.2 to 0.7) for brachial diastolic BP ( P =0.12), -7.5 mm Hg (95% CI, -14.4 to -0.6) for aortic systolic BP ( P =0.03), -5.7 mm Hg (95% CI, -10.8 to -0.6) for augmentation index ( P =0.03), -0.3 m/s (95% CI, -0.6 to -0.1) for pulse wave velocity ( P =0.02), -8.6 mm Hg (95% CI, -15.4 to -1.9) for peak reservoir pressure ( P =0.01), and -3.6 mm Hg (95% CI, -6.3 to -0.8) for backward pressure amplitude ( P =0.01)., Conclusions: Monthly, high-dose, 1-year vitamin D supplementation lowered central BP parameters among adults with vitamin D deficiency but not in the total sample., Clinical Trial Registration: URL: http://www.anzctr.org.au. Unique identifier: ACTRN12611000402943., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Objectives: This study investigated whether wave reflection measured by wave intensity analysis predicts future cardiovascular events in individuals with hypertension and sought to establish whether this relationship is independent of other cardiovascular risk factors and is associated with evidence of increased load on the left ventricle., Background: Wave reflection may impose an additional load on the left ventricle, and augmentation index, a surrogate of wave reflection, has been reported to predict cardiovascular events in some, but not all studies., Methods: Measurements of brachial and carotid blood pressure (BP) measurement, carotid ultrasound, echocardiography, and blood chemistry analyses were performed on 259 ASCOT (Anglo Scandinavian Cardiac Outcomes Trial) participants approximately 1 year after randomization, and wave intensity analysis was used to calculate wave reflection index (WRI), the ratio of peak forward to peak backward pressure (P(b)/P(f)), and carotid augmentation index (cAI(x)). All participants were followed up for a median period of 5.9 years, accruing 33 cardiovascular events., Results: WRI, P(b)/P(f), and to a lesser extent, cAI(x), were correlated. WRI predicted cardiovascular events (hazard ratio: 2.10; 95% confidence interval: 1.10 to 3.99; p = 0.02) in an unadjusted model. Multivariate analysis showed that this association was independent of BP. P(b)/P(f) and cAI(x) did not significantly predict cardiovascular events. WRI was also positively associated with increased left ventricular mass index and elevated B-type natriuretic peptide adjusted for age and sex, and these associations were independent of BP or other cardiovascular risk factors., Conclusions: Higher wave reflection predicts future cardiovascular events independent of conventional risk factors in people with treated hypertension., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Patients with controlled hypertension are at risk of future cardiac events, but predicting first events remains difficult. We hypothesized that modern echocardiographic measures of left ventricular diastolic function may be more sensitive than traditional echocardiographic methods of risk prediction and set out to test this in a cohort of patients with well-controlled hypertension., Methods and Results: Conventional and tissue Doppler echocardiography was performed on 980 participants in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). All subjects had hypertension, but no known cardiac disease. Cardiac events were defined as fatal and non-fatal myocardial infarction (including silent myocardial infarction), coronary revascularization procedures, new-onset angina (stable or unstable), fatal and non-fatal heart failure, and life-threatening arrhythmias. Analysis was performed by a single, blinded observer. There were 56 primary cardiac events during 4.2 +/- 0.7 years follow-up. The ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity (E/E') was the strongest predictor of first cardiac events in Cox-proportional hazards models. Following adjustment for covariates, a unit rise in the E/E' ratio was associated with a 17% increment in risk of a cardiac event (HR 1.17, CI 1.05-1.29; P = 0.003)., Conclusion: Tissue Doppler E/E', a non-invasive estimate of left atrial filling pressure, independently predicts primary cardiac events in a hypertensive population and out-performed traditional echocardiographic measures in this moderately sized, well-treated hypertensive population. E/E' represents a simple, effective tool for assessing cardiac risk in a hypertensive population.

The ADVANCE Retinal Measurements (AdRem) Study is a large intervention study evaluating the effects of target driven intensive glucose control and placebo controlled blood pressure lowering on retinal vascular changes. AdRem is a sub-study of the ADVANCE Study (Action in Diabetes and Vascular disease), a 2x2 factorial randomized controlled trial with an ACE inhibitor-diuretic combination (perindopril-indapamide) and a gliclazide MR-based regimen in patients with type 2 diabetes mellitus. The AdRem study is based on seven-field stereoscopic retinal photographs of both eyes. These are taken within 3 months after randomization in ADVANCE (baseline), at the biennial and at the final visit. The primary outcome is progression of two or more steps in ETDRS classification. Secondary outcomes include progression of retinal vascular lesions and distortion of retinal vascular geometry. Retinal photographs are made on film and digitized at a central laboratory. The AdRem study uses fully digitized quality control and grading. Between August 2002 and January 2004 1978 patients were included in the AdRem study, from 39 centers in 14 countries. Approximately 85% comply with the strict AdRem quality requirements. Publication of the results is expected in early 2008. The AdRem study is designed to provide reliable evidence on the effects of intensive glucose control and blood pressure lowering on both diabetic retinopathy and abnormalities of retinal vasculature in patients with type 2 diabetes mellitus.

Objective: Grading of hypertension severity by fundoscopic appearance is difficult and inaccurate. We investigated whether essential hypertension (EHT) and malignant phase hypertension (MHT) were associated with quantifiable abnormalities of the topology and architecture of the retinal circulation., Methods: The topology and architecture of the retinal microvasculature were compared in images from 20 normotensive subjects, 20 patients with EHT and 20 patients with MHT. Digitized retinal photographs were analysed by a novel multiscale image analysis method using a semi-automated program to quantify geometrical and topological properties of arteriolar and venular trees., Results: EHT was associated with an increase in the arteriolar length-to-diameter ratio (P < 0.01). There were also alterations in arteriolar topology indicative of rarefaction, including a marked reduction in the number of terminal branches in EHT (P < 0.01). These changes in the arteriolar network were exaggerated in MHT and there was also increased venular tortuosity and venular rarefaction in MHT compared with normotensive subjects., Conclusions: Hypertension is associated with marked topological alterations in the retinal vasculature, and quantification of these changes may be a useful novel approach to the assessment of target organ damage in hypertension.

Excess pressure integral (XSPI), a new index of surplus work performed by the left ventricle, can be calculated from blood pressure waveforms and may indicate circulatory dysfunction. We investigated whether XSPI predicted future cardiovascular events and target organ damage in treated hypertensive individuals. Radial blood pressure waveforms were acquired by tonometry in 2069 individuals (aged, 63±8 years) in the Conduit Artery Functional Evaluation (CAFE) substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Measurements of left ventricular mass index (n=862) and common carotid artery intima media thickness (n=923) were also performed. XSPI and the integral of reservoir pressure were lower in people treated with amlodipine±perindopril than in those treated with atenolol±bendroflumethiazide, although brachial systolic blood pressure was similar. A total of 134 cardiovascular events accrued during a median 3.4 years of follow-up; XSPI was a significant predictor of cardiovascular events after adjustment for age and sex, and this relationship was unaffected by adjustment for conventional cardiovascular risk factors or Framingham risk score. XSPI, central systolic blood pressure, central augmentation pressure, central pulse pressure, and integral of reservoir pressure were correlated with left ventricular mass index, but only XSPI, augmentation pressure, and central pulse pressure were associated positively with carotid artery intima media thickness. Associations between left ventricular mass index, XSPI, and integral of reservoir pressure and carotid artery intima media thickness and XSPI were unaffected by multivariable adjustment for other covariates. XSPI is a novel indicator of cardiovascular dysfunction and independently predicts cardiovascular events and targets organ damage in a prospective clinical trial. [ABSTRACT FROM AUTHOR]

Objectives: We hypothesized that an amlodipine-based regimen would have more favorable effects on left ventricular (LV) diastolic function. Background: Different antihypertensive therapies may vary in their effect on LV diastolic function. Methods: The HACVD (Hypertension Associated Cardiovascular Disease) substudy of ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) collected detailed cardiovascular phenotypic data on a subset of 1,006 participants recruited from 2 centers (St. Mary''s Hospital, London, and Beaumont Hospital, Dublin). Conventional and tissue Doppler echocardiography and measurement of plasma B-type natriuretic peptide (BNP) were performed approximately 1 year after randomization to atenolol-based or amlodipine-based antihypertensive treatment to assess LV diastolic function. Results: On-treatment blood pressure (BP) (mean ± SD) was similar in both groups: atenolol-based regimen, systolic BP of 137 ± 17 mm Hg, diastolic BP of 82 ± 9 mm Hg; amlodipine-based regimen, systolic BP of 136 ± 15 mm Hg, diastolic BP of 80 ± 9 mm Hg. Ejection fraction did not differ between groups, but early diastolic mitral annular velocity (E′), a measure of diastolic relaxation, was lower in patients on the atenolol-based regimen: atenolol-based regimen, 7.9 ± 1.8; amlodipine-based regimen, 8.8 ± 2.0. A measure of left ventricular filling pressure, E/E′, and BNP were significantly higher in patients on the atenolol-based regimen. Differences in E′, E/E′, and BNP remained significant after adjustment for age and sex. Further adjustment for systolic BP, LV mass index, and heart rate had no impact on differences in mean E′ or BNP. The difference in E/E′ was attenuated. Conclusions: Patients receiving treatment with an amlodipine-based regimen had better diastolic function than patients treated with the atenolol-based regimen. Treatment-related differences in diastolic function were independent of BP reduction and other factors that are known to affect diastolic function. [Copyright &y& Elsevier]