Elevated Aortic Pulse Wave Velocity, a Marker of Arterial Stiffness, Predicts Cardiovascular Events in Well-Functioning Older Adults

Sutton-Tyrrell, Kim; Najjar, Samer S.; Boudreau, Robert M.; Venkitachalam, Lakshmi; Kupelian, Varant; Simonsick, Eleanor M.; Havlik, Richard J.; Lakatta, Edward G.; Spurgeon, Harold A.; Kritchevsky, Stephen B.; Pahor, Marco; Bauer, Douglas C.; Newman, Anne B.

doi:10.1161/circulationaha.104.483628

Cited by 1,120 publications

(871 citation statements)

References 60 publications

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“…In aortic PWV studies, MI was often included in the definition of outcome variables such as overall CVD events or CHD, but not investigated as an individual outcome as has been done in this study. These previous studies show an association between aortic PWV and CHD,8, 31, 32, 33 as is shown here as well. Our results are consistent with previous PP studies that reported associations with both incident MI3 and CHD34 after adjustment for traditional CVD risk factors in a hypertensive and community‐based cohort, respectively.…”

Section: Discussionsupporting

confidence: 92%

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Relationship of Arterial Stiffness Index and Pulse Pressure With Cardiovascular Disease and Mortality

Said

Eppinga

Lipšic

et al. 2018

JAHA

170

131

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BackgroundVascular aging results in stiffer arteries and may have a role in the development of cardiovascular disease (CVD). Arterial stiffness index (ASI), measured by finger photoplethysmography, and pulse pressure (PP) are 2 independent vascular aging indices. We investigated whether ASI or PP predict new‐onset CVD and mortality in a large community‐based population.Methods and ResultsWe studied 169 613 UK Biobank participants (mean age 56.8 years; 45.8% males) who underwent ASI measurement and blood pressure measurement for PP calculation. Mean±SD ASI was 9.30±3.1 m/s and mean±SD PP was 50.98±13.2 mm Hg. During a median disease follow‐up of 2.8 years (interquartile range 1.4–4.0), 18 190 participants developed CVD, of which 1587 myocardial infarction (MI), 4326 coronary heart disease, 1192 heart failure, and 1319 stroke. During a median mortality follow‐up of 6.1 years (interquartile range 5.8–6.3), 3678 participants died, of which 1180 of CVD. Higher ASI was associated with increased risk of overall CVD (unadjusted hazard ratio 1.27; 95% confidence interval [CI], 1.25–1.28), myocardial infarction (1.38; 95% CI, 1.32–1.44), coronary heart disease (1.31; 95% CI, 1.27–1.34), and heart failure (1.31; 95% CI 1.24–1.37). ASI also predicted mortality (all‐cause, CVD, other). Higher PP was associated with overall CVD (1.57; 95% CI, 1.55–1.59), myocardial infarction (1.48; 95% CI, 1.42–1.54), coronary heart disease (1.47; 95% CI, 1.43–1.50), heart failure (1.47; 95% CI, 1.40–1.55), and CVD mortality (1.47; 95% CI, 1.40–1.55). PP improved risk reclassification of CVD in a non–laboratory‐based Framingham Risk Score by 5.4%, ASI by 2.3%.Conclusions ASI and PP are independent predictors of CVD and mortality outcomes. Although both improved risk prediction for new‐onset disease, PP appears to have a larger clinical value than ASI.

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Section: Discussionsupporting

confidence: 92%

“…The association between aortic PWV with HF is inconsistent across studies 32, 35. We found an association between ASI and HF after adjustment for traditional CVD risk factor but it had little discriminating power.…”

Section: Discussioncontrasting

confidence: 62%

Relationship of Arterial Stiffness Index and Pulse Pressure With Cardiovascular Disease and Mortality

Said

Eppinga

Lipšic

et al. 2018

JAHA

170

131

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“…Increased stiffening of the large elastic arteries occurs with advancing age and is a major independent risk factor for age‐associated CV events and clinical CVD (Reddy et al ., 2003; Sutton‐Tyrrell et al ., 2005; Fleenor et al ., 2012b). Increased aortic stiffness, in particular, reduces the ability to buffer increases in pressure produced by systolic ejection of blood into the large elastic arteries with each cardiac contraction.…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice

et al. 2016

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SummaryWe tested the hypothesis that supplementation of nicotinamide mononucleotide (NMN), a key NAD + intermediate, increases arterial SIRT1 activity and reverses age‐associated arterial dysfunction and oxidative stress. Old control mice (OC) had impaired carotid artery endothelium‐dependent dilation (EDD) (60 ± 5% vs. 84 ± 2%), a measure of endothelial function, and nitric oxide (NO)‐mediated EDD (37 ± 4% vs. 66 ± 6%), compared with young mice (YC). This age‐associated impairment in EDD was restored in OC by the superoxide (O2−) scavenger TEMPOL (82 ± 7%). OC also had increased aortic pulse wave velocity (aPWV, 464 ± 31 cm s−1 vs. 337 ± 3 cm s−1) and elastic modulus (EM, 6407 ± 876 kPa vs. 3119 ± 471 kPa), measures of large elastic artery stiffness, compared with YC. OC had greater aortic O2− production (2.0 ± 0.1 vs. 1.0 ± 0.1 AU), nitrotyrosine abundance (a marker of oxidative stress), and collagen‐I, and reduced elastin and vascular SIRT1 activity, measured by the acetylation status of the p65 subunit of NFκB, compared with YC. Supplementation with NMN in old mice restored EDD (86 ± 2%) and NO‐mediated EDD (61 ± 5%), reduced aPWV (359 ± 14 cm s−1) and EM (3694 ± 315 kPa), normalized O2− production (0.9 ± 0.1 AU), decreased nitrotyrosine, reversed collagen‐I, increased elastin, and restored vascular SIRT1 activity. Acute NMN incubation in isolated aortas increased NAD + threefold and manganese superoxide dismutase (MnSOD) by 50%. NMN supplementation may represent a novel therapy to restore SIRT1 activity and reverse age‐related arterial dysfunction by decreasing oxidative stress.

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“…Most of these studies have performed only one PWV measurement as it is not otherwise stated. 1,3,[17][18][19][20][21][22][23][24][25][26][27][28] One study reported that one PWV measurement was performed 29 and two studies 30,31 referred that two and three PWV measurements were performed, respectively, and an average value was then calculated. Thus, based on the results of this study, a substantial variation (and 'bias') in the determined CVR and the calculated statistical measures may exist, which depends on the number of PWV measurements.…”

Section: Discussionmentioning

confidence: 99%

Assessment of differences between repeated pulse wave velocity measurements in terms of ‘bias’ in the extrapolated cardiovascular risk and the classification of aortic stiffness: Is a single PWV measurement enough?

et al. 2011

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Currently, there is no recommendation regarding the minimum number of pulse wave velocity (PWV) measurements to optimize individual's cardiovascular risk (CVR) stratification. The aim of this study was to examine differences between three single consecutive and averaged PWV measurements in terms of the extrapolated CVR and the classification of aortic stiffness as normal. In 60 subjects who referred for CVR assessment, three repeated measurements of blood pressure (BP), heart rate and PWV were performed. The reproducibility was evaluated by the intraclass correlation coefficient (ICC) and mean±s.d. of differences. The absolute differences between single and averaged PWV measurements were classified as: p0.25, 0.26-0.49, 0.50-0.99 and X1 m s À1 . A difference X0.5 m s À1 (corresponding to 7.5% change in CVR, metaanalysis data from 412 000 subjects) was considered as clinically meaningful; PWV values (single or averaged) were classified as normal according to respective age-corrected normal values (European Network data). Kappa statistic was used to evaluate the agreement between classifications. PWV for the first, second and third measurement was 7.0±1.9, 6.9±1.9, 6.9±2.0 m s À1 , respectively (P ¼ 0.319); BP and heart rate did not vary significantly. A good reproducibility between single measurements was observed (ICC40.94, s.d. ranged between 0.43 and 0.64 m s À1 ). A high percent with difference X0.5 m s À1 was observed between: any pair of the three single PWV measurements (26.6-38.3%); the first or second single measurement and the average of the first and second (18.3%); any single measurement and the average of three measurements (10-20%). In only up to 5% a difference X0.5 m s À1 was observed between the average of three and the average of any two PWV measurements. There was no significant agreement regarding PWV classification as normal between: the first or second measurement and the averaged PWV values. There was significant agreement in classification made by the average of the first two and the average of three PWV measurements (j ¼ 0.85, Po0.001). Even when high reproducibility in PWV measurement is succeeded single measurements provide quite variable results in terms of the extrapolated CVR and the classification of aortic stiffness as normal. The average of two PWV measurements provides similar results with the average of three.

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Elevated Aortic Pulse Wave Velocity, a Marker of Arterial Stiffness, Predicts Cardiovascular Events in Well-Functioning Older Adults

Cited by 1,120 publications

References 60 publications

Relationship of Arterial Stiffness Index and Pulse Pressure With Cardiovascular Disease and Mortality

Relationship of Arterial Stiffness Index and Pulse Pressure With Cardiovascular Disease and Mortality

Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice

Assessment of differences between repeated pulse wave velocity measurements in terms of ‘bias’ in the extrapolated cardiovascular risk and the classification of aortic stiffness: Is a single PWV measurement enough?

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