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      Identification of Distinct Arterial Waveform Clusters and a Longitudinal Evaluation of Their Clinical Usefulness

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          Abstract

          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.

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          Most cited references32

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          Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis.

          The purpose of this study was to calculate robust quantitative estimates of the predictive value of aortic pulse wave velocity (PWV) for future cardiovascular (CV) events and all-cause mortality by meta-analyses of longitudinal studies. Arterial stiffness is increasingly recognized as a surrogate end point for CV disease. We performed a meta-analysis of 17 longitudinal studies that evaluated aortic PWV and followed up 15,877 subjects for a mean of 7.7 years. The pooled relative risk (RR) of clinical events increased in a stepwise, linear-like fashion from the first to the third tertile of aortic PWV. The pooled RRs of total CV events, CV mortality, and all-cause mortality were 2.26 (95% confidence interval: 1.89 to 2.70, 14 studies), 2.02 (95% confidence interval: 1.68 to 2.42, 10 studies), and 1.90 (95% confidence interval: 1.61 to 2.24, 11 studies), respectively, for high versus low aortic PWV subjects. For total CV events and CV mortality, the RR was significantly higher in high baseline risk groups (coronary artery disease, renal disease, hypertension) compared with low-risk subjects (general population). An increase in aortic PWV by 1 m/s corresponded to an age-, sex-, and risk factor-adjusted risk increase of 14%, 15%, and 15% in total CV events, CV mortality, and all-cause mortality, respectively. An increase in aortic PWV by 1 SD was associated with respective increases of 47%, 47%, and 42%. Aortic stiffness expressed as aortic PWV is a strong predictor of future CV events and all-cause mortality. The predictive ability of arterial stiffness is higher in subjects with a higher baseline CV risk.
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            Dose-response analyses using restricted cubic spline functions in public health research.

            Taking into account a continuous exposure in regression models by using categorization, when non-linear dose-response associations are expected, have been widely criticized. As one alternative, restricted cubic spline (RCS) functions are powerful tools (i) to characterize a dose-response association between a continuous exposure and an outcome, (ii) to visually and/or statistically check the assumption of linearity of the association, and (iii) to minimize residual confounding when adjusting for a continuous exposure. Because their implementation with SAS® software is limited, we developed and present here an SAS macro that (i) creates an RCS function of continuous exposures, (ii) displays graphs showing the dose-response association with 95 per cent confidence interval between one main continuous exposure and an outcome when performing linear, logistic, or Cox models, as well as linear and logistic-generalized estimating equations, and (iii) provides statistical tests for overall and non-linear associations. We illustrate the SAS macro using the third National Health and Nutrition Examination Survey data to investigate adjusted dose-response associations (with different models) between calcium intake and bone mineral density (linear regression), folate intake and hyperhomocysteinemia (logistic regression), and serum high-density lipoprotein cholesterol and cardiovascular mortality (Cox model). 2010 John Wiley & Sons, Ltd.
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              Effects of an Angiotensin-Converting–Enzyme Inhibitor, Ramipril, on Cardiovascular Events in High-Risk Patients

              Angiotensin-converting-enzyme inhibitors improve the outcome among patients with left ventricular dysfunction, whether or not they have heart failure. We assessed the role of an angiotensin-converting-enzyme inhibitor, ramipril, in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart failure. A total of 9297 high-risk patients (55 years of age or older) who had evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low ejection fraction or heart failure were randomly assigned to receive ramipril (10 mg once per day orally) or matching placebo for a mean of five years. The primary outcome was a composite of myocardial infarction, stroke, or death from cardiovascular causes. The trial was a two-by-two factorial study evaluating both ramipril and vitamin E. The effects of vitamin E are reported in a companion paper. A total of 651 patients who were assigned to receive ramipril (14.0 percent) reached the primary end point, as compared with 826 patients who were assigned to receive placebo (17.8 percent) (relative risk, 0.78; 95 percent confidence interval, 0.70 to 0.86; P<0.001). Treatment with ramipril reduced the rates of death from cardiovascular causes (6.1 percent, as compared with 8.1 percent in the placebo group; relative risk, 0.74; P<0.001), myocardial infarction (9.9 percent vs. 12.3 percent; relative risk, 0.80; P<0.001), stroke (3.4 percent vs. 4.9 percent; relative risk, 0.68; P<0.001), death from any cause (10.4 percent vs. 12.2 percent; relative risk, 0.84; P=0.005), revascularization procedures (16.3 percent vs. 18.8 percent; relative risk, 0.85; P<0.001), cardiac arrest (0.8 percent vs. 1.3 percent; relative risk, 0.62; P=0.02), [corrected] heart failure (9.1 percent vs. 11.6 percent; relative risk, 0.77; P<0.001), and complications related to diabetes (6.4 percent vs. 7.6 percent; relative risk, 0.84; P=0.03). Ramipril significantly reduces the rates of death, myocardial infarction, and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure.
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                Author and article information

                Journal
                Hypertension
                Hypertension
                Ovid Technologies (Wolters Kluwer Health)
                0194-911X
                1524-4563
                October 2019
                October 2019
                : 74
                : 4
                : 921-928
                Affiliations
                [1 ]From the School of Population Health, University of Auckland, New Zealand (J.D.S., R.S.)
                [2 ]Department of Population Science &amp; Experimental Medicine, Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, United Kingdom (A.D.H.)
                [3 ]MRC Unit for Lifelong Health and Ageing at UCL, London, United Kingdom (A.D.H.)
                [4 ]Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (C.A.C.)
                [5 ]International Centre for Circulatory Health (S.A.M.T.), Imperial College, London, United Kingdom
                [6 ]Department of Bioengineering (K.H.P.), Imperial College, London, United Kingdom
                [7 ]Center for Health &amp; Bioresources, AIT Austrian Institute of Technology, Vienna, Austria (B.H., S.W.).
                Article
                10.1161/HYPERTENSIONAHA.119.12625
                6742504
                31446803
                68200244-a553-4403-82ff-c724d6cbe11c
                © 2019
                History

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