Heterogeneity in age related central arterial stiffening: ascending aortic stiffness is a better predictor of carotid to femoral pulse wave velocity and brachial peripheral blood pressure than carotid stiffness

Carotid-femoral pulse wave velocity (PWV) has emerged as the gold standard for non-invasive evaluation of aortic stiffness; absence of standardized methodologies of study and lack of normal and reference values have limited a wider clinical implementation. This work was carried out in a Uruguayan (South American) population in order to characterize normal, reference, and threshold levels of PWV considering normal age-related changes in PWV and the prevailing blood pressure level during the study. A conservative approach was used, and we excluded symptomatic subjects; subjects with history of cardiovascular (CV) disease, diabetes mellitus or renal failure; subjects with traditional CV risk factors (other than age and gender); asymptomatic subjects with atherosclerotic plaques in carotid arteries; patients taking anti-hypertensives or lipid-lowering medications. The included subjects (n=429) were categorized according to the age decade and the blood pressure levels (at study time). All subjects represented the “reference population”; the group of subjects with optimal/normal blood pressures levels at study time represented the “normal population.”Results. Normal and reference PWV levels were obtained. Differences in PWV levels and aging-associated changes were obtained. The obtained data could be used to define vascular aging and abnormal or disease-related arterial changes.

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Spironolactone Reduces Aortic Stiffness in Patients With Resistant Hypertension Independent of Blood Pressure Change

Journal of the American Heart Association ◽

10.1161/jaha.120.019434 ◽

2021 ◽

Author(s):

Sudeep R. Aryal ◽

Mohammed Siddiqui ◽

Oleg F. Sharifov ◽

Megan D. Coffin ◽

Bin Zhang ◽

...

Keyword(s):

Blood Pressure ◽

Pulse Wave Velocity ◽

Wave Velocity ◽

Resistant Hypertension ◽

Aortic Stiffness ◽

Pulse Wave ◽

Antihypertensive Medications ◽

Mineralocorticoid Receptor Antagonist ◽

Stiffness Reduction ◽

Arterial Blood

Background Aortic stiffness is an independent predictor of cardiovascular events in patients with arterial hypertension. Resistant hypertension is often linked to hyperaldosteronism and associated with adverse outcomes. Spironolactone, a mineralocorticoid receptor antagonist, has been shown to reduce both the arterial blood pressure (BP) and aortic stiffness in resistant hypertension. However, the mechanism of aortic stiffness reduction by spironolactone is not well understood. We hypothesized that spironolactone reduces aortic stiffness in resistant hypertension independently of BP change. Methods and Results Patients with uncontrolled BP (≥140/90 mm Hg) despite use of ≥3 antihypertensive medications (including diuretics) were prospectively recruited. Participants were started on spironolactone at 25 mg/d, and increased to 50 mg/d at 4 weeks while other antihypertensive medications were withdrawn to maintain constant mean BP. Phase‐contrast cardiac magnetic resonance imaging of the ascending aorta was performed in 30 participants at baseline and after 6 months of spironolactone treatment to measure aortic pulsatility, distensibility, and pulse wave velocity. Pulse wave velocity decreased (6.3±2.3 m/s to 4.5±1.8 m/s, P <0.001) and pulsatility and distensibility increased (15.9%±5.3% to 22.1%±7.9%, P <0.001; and 0.28%±0.10%/mm Hg to 0.40%±0.14%/mm Hg, P <0.001, respectively) following 6 months of spironolactone. Conclusions Our results suggest that spironolactone improves aortic properties in resistant hypertension independently of BP, which may support the hypothesis of an effect of aldosterone on the arterial wall. A larger prospective study is needed to confirm our findings.

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The influence of resting heart rate on pulse wave velocity measurement is mediated by blood pressure and depends on aortic stiffness levels: insights from the Corinthia study

Physiological Measurement ◽

10.1088/1361-6579/ab165f ◽

2019 ◽

Vol 40 (5) ◽

pp. 055005 ◽

Cited By ~ 14

Author(s):

Theodore G Papaioannou ◽

Evangelos Oikonomou ◽

George Lazaros ◽

Evangelia Christoforatou ◽

Georgia Vogiatzi ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Pulse Wave Velocity ◽

Wave Velocity ◽

Velocity Measurement ◽

Aortic Stiffness ◽

Pulse Wave ◽

Resting Heart Rate ◽

Pulse Wave Velocity Measurement

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Mitochondria-targeted antioxidant therapy with MitoQ ameliorates aortic stiffening in old mice

Journal of Applied Physiology ◽

10.1152/japplphysiol.00670.2017 ◽

2018 ◽

Vol 124 (5) ◽

pp. 1194-1202 ◽

Cited By ~ 38

Author(s):

Rachel A. Gioscia-Ryan ◽

Micah L. Battson ◽

Lauren M. Cuevas ◽

Jason S. Eng ◽

Michael P. Murphy ◽

...

Keyword(s):

Pulse Wave Velocity ◽

Wave Velocity ◽

Aortic Stiffness ◽

Pulse Wave ◽

Therapeutic Strategies ◽

Elastin Degradation ◽

Age Related ◽

Clinical Disorders ◽

Aortic Stiffening ◽

Old Mice

Aortic stiffening is a major independent risk factor for cardiovascular diseases, cognitive dysfunction, and other chronic disorders of aging. Mitochondria-derived reactive oxygen species are a key source of arterial oxidative stress, which may contribute to arterial stiffening by promoting adverse structural changes—including collagen overabundance and elastin degradation—and enhancing inflammation, but the potential for mitochondria-targeted therapeutic strategies to ameliorate aortic stiffening with primary aging is unknown. We assessed aortic stiffness [pulse-wave velocity (aPWV)], ex vivo aortic intrinsic mechanical properties [elastic modulus (EM) of collagen and elastin regions], and aortic protein expression in young (~6 mo) and old (~27 mo) male C57BL/6 mice consuming normal drinking water (YC and OC) or water containing mitochondria-targeted antioxidant MitoQ (250 µM; YMQ and OMQ) for 4 wk. Both baseline and postintervention aPWV values were higher in OC vs. YC (post: 482 ± 21 vs. 420 ± 5 cm/s, P < 0.05). MitoQ had no effect in young mice but decreased aPWV in old mice (OMQ, 426 ± 20, P < 0.05 vs. OC). MitoQ did not affect age-associated increases in aortic collagen-region EM, collagen expression, or proinflammatory cytokine expression, but partially attenuated age-associated decreases in elastin region EM and elastin expression. Our results demonstrate that MitoQ reverses in vivo aortic stiffness in old mice and suggest that mitochondria-targeted antioxidants may represent a novel, promising therapeutic strategy for decreasing aortic stiffness with primary aging and, possibly, age-related clinical disorders in humans. The destiffening effects of MitoQ treatment may be at least partially mediated by attenuation/reversal of age-related aortic elastin degradation. NEW & NOTEWORTHY We show that 4 wk of treatment with the mitochondria-specific antioxidant MitoQ in mice completely reverses the age-associated elevation in aortic stiffness, assessed as aortic pulse-wave velocity. The destiffening effects of MitoQ treatment may be at least partially mediated by attenuation of age-related aortic elastin degradation. Our results suggest that mitochondria-targeted therapeutic strategies may hold promise for decreasing arterial stiffening with aging in humans, possibly decreasing the risk of many chronic age-related clinical disorders.

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Effects of a Low‐Salt and High‐Potassium Diet on Arterial Stiffness and Left Ventricular Function in Indigenous Papuans

Journal of the American Heart Association ◽

10.1161/jaha.121.021789 ◽

2021 ◽

Author(s):

Akio Ishida ◽

Akihiro Isotani ◽

Michiko Fujisawa ◽

Eva Garcia del Saz ◽

Kiyohito Okumiya ◽

...

Keyword(s):

Blood Pressure ◽

Pulse Wave Velocity ◽

Diastolic Function ◽

Wave Velocity ◽

Pulse Wave ◽

Left Ventricular ◽

Lv Function ◽

High Potassium ◽

Age Related ◽

Lv Diastolic Function

Background A sodium‐restricted diet represents a potential non‐pharmacological strategy for improving blood pressure, arterial stiffness, and left ventricular (LV) diastolic function. We investigated age‐related differences in LV structure and function and the relationship between LV function and central hemodynamics in an indigenous Papuan population, who maintain a traditional lifestyle, including a low‐salt and high‐potassium diet. Methods and Results We measured LV dimensions, transmitral blood flow, and mitral annular tissue velocities through echocardiography and Doppler imaging. Blood pressure and brachial‐ankle pulse wave velocity were measured using an automatic device (Omron). Central blood pressure and wave reflection parameters were estimated via oscillometry (Mobil‐O‐Graph, using European calibrations). A total of 82 native Papuans (median age, 42 years; 38 women; no blood pressure treatment) were enrolled. Age‐related difference in brachial systolic pressure was modest but significant, and brachial‐ankle pulse wave velocity significantly increased with age; however, LV mass index remained unchanged. LV ejection fraction and global longitudinal strain were preserved; mitral A‐wave velocity and average E/e´ increased; and e´ and E/A decreased with age. Brachial‐ankle pulse wave velocity and spot urine Na/K were positively and independently correlated with E/e´. Age and heart rate were inversely associated with E/A. In conclusion, LV systolic function was preserved; however, LV diastolic function decreased with age in Papuans. Moreover, age‐related arterial stiffening, but not wave reflections, was inversely related to LV diastolic function. Conclusions Our results suggest that arterial and LV stiffness may not be altered by sodium restriction. Longitudinal studies are warranted to elucidate the effects of diet on arterial and LV function.

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Abstract 543: Increased Aortic Pulse Wave Velocity in Type 2 Diabetic db/db Mice is Dependent on Blood Pressure

Hypertension ◽

10.1161/hyp.64.suppl_1.543 ◽

2014 ◽

Vol 64 (suppl_1) ◽

Author(s):

Mircea Anghelescu ◽

Keith J Gooch ◽

Aaron J Trask

Keyword(s):

Blood Pressure ◽

Pulse Wave Velocity ◽

Wave Velocity ◽

Aortic Stiffness ◽

Pulse Wave ◽

Ex Vivo ◽

Aortic Pulse Wave Velocity ◽

Type 2 Diabetic

Pulse wave velocity (PWV) is the gold standard for in vivo aortic stiffness measurements but can be dependent upon blood pressure and/or heart rate. Previous studies from our and other labs have shown increased aortic PWV in type 2 diabetic db/db mice. Moreover, preliminary ex vivo pressure myography data from our lab has also shown a lack of increase in passive aortic stiffness, suggesting that increased PWV in vivo , and therefore, increased stiffness in db/db mice may be dependent upon other mechanisms. In this study, we tested the hypothesis that increased aortic pulse wave velocity measured in db/db mice in vivo is blood pressure dependent under anesthesia. 16-wk old normal Db/db (n=9) and type 2 diabetic db/db (n=5) mice were anesthetized with 2% isoflurane and instrumented with two 1.2F pressure-tip catheters: one inserted in the left carotid artery and advanced to the thoracic aorta, the other inserted into the left femoral artery and advanced into the abdominal aorta. Blood pressure was continuously recorded and PWV was calculated using the foot-to-foot method. A microcannula was inserted into the right jugular vein for the administration of drugs. After a stabilization period of 25-30 mins, baseline BPs and PWVs were measured, after which mice were infused with increasing doses of phenylephrine (Phe, 100-500 nmol/kg/min) and sodium nitroprusside (SNP, 100-500 nmol/kg/min) to increase and decrease blood pressure, respectively. At baseline (prior to the infusion of any drugs), mean arterial pressure and aortic PWV were significantly elevated in db/db mice under anesthesia (MAP; Db/db: 77±5 vs. db/db: 100±4 mmHg, p <0.05; PWV; Db/db: 0.31±0.01 vs. db/db: 0.35±0.01 cm/ms, p <0.05). The increase in aortic PWV in db/db mice at baseline was completely abrogated when measured at equivalent MAPs ranging from 40-120 mmHg during the Phe and SNP infusions ( p >0.05). In both Db/db and db/db mice, aortic PWV was significantly correlated with MAP (Db/db: r=0.94, p <0.001; db/db: r=0.97, p <0.0001). These data show that increased aortic PWV, and therefore increased aortic stiffness in db/db mice in vivo is dependent upon blood pressure.

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SBP, DBP, and pulse blood pressure variability are temporally associated with the increase in pulse wave velocity in a model of aortic stiffness

Journal of Hypertension ◽

10.1097/hjh.0000000000000838 ◽

2016 ◽

Vol 34 (4) ◽

pp. 666-675 ◽

Cited By ~ 3

Author(s):

Marc Isabelle ◽

Stefano Chimenti ◽

Hélène Beaussier ◽

Denis Gransagne ◽

Nicole Villeneuve ◽

...

Keyword(s):

Blood Pressure ◽

Pulse Wave Velocity ◽

Wave Velocity ◽

Blood Pressure Variability ◽

Aortic Stiffness ◽

Pulse Wave

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Beat-to-Beat Blood Pressure Variability in the First Trimester Is Associated With the Development of Preeclampsia in a Prospective Cohort

Hypertension ◽

10.1161/hypertensionaha.120.15019 ◽

2020 ◽

Vol 76 (6) ◽

pp. 1800-1807 ◽

Cited By ~ 1

Author(s):

Virginia R. Nuckols ◽

Seth W. Holwerda ◽

Rachel E. Luehrs ◽

Lyndsey E. DuBose ◽

Amy K. Stroud ◽

...

Keyword(s):

Blood Pressure ◽

Pulse Wave Velocity ◽

Wave Velocity ◽

Blood Pressure Variability ◽

Aortic Stiffness ◽

Baroreflex Sensitivity ◽

Pulse Wave ◽

First Trimester ◽

Study Cohort ◽

Hypertensive Disorder

Women with preeclampsia, a hypertensive disorder of pregnancy, exhibit greater beat-to-beat blood pressure variability (BPV) in the third trimester after clinical onset of the disorder. However, it remains unknown whether elevated BPV precedes the development of preeclampsia. A prospective study cohort of 139 women (age 30.2±4.0 years) were enrolled in early pregnancy (<14 weeks gestation). BPV was quantified by time domain analyses of 10-minute continuous beat-to-beat blood pressure recordings via finger photoplethysmography in the first, second, and third trimesters. Aortic stiffness (carotid-femoral pulse wave velocity) and spontaneous cardiovagal baroreflex sensitivity were also measured each trimester. Eighteen women (13%) developed preeclampsia. Systolic BPV was higher in all trimesters among women who developed versus did not develop preeclampsia (first: 4.8±1.3 versus 3.7±1.2, P =0.001; second: 5.1±1.8 versus 3.8±1.1, P =0.02; third: 5.2±0.8 versus 4.0±1.1 mm Hg, P =0.002). Elevated first trimester systolic BPV was associated with preeclampsia (odds ratio, 1.94 [95% CI, 1.27–2.99]), even after adjusting for risk factors (age, body mass index, systolic blood pressure, history of preeclampsia, and diabetes mellitus) and was a significant predictor of preeclampsia (area under the receiver operator characteristic curve=0.75±0.07; P =0.002). Carotid-femoral pulse wave velocity was elevated in the first trimester among women who developed preeclampsia (5.9±0.8 versus 5.2±0.8 m/s; P =0.002) and was associated with BPV after adjustment for mean blood pressure ( r =0.26; P =0.005). First trimester baroreflex sensitivity did not differ between groups ( P =0.23) and was not related to BPV ( P =0.36). Elevated systolic BPV is independently associated with the development of preeclampsia as early as the first trimester, possibly mediated in part by higher aortic stiffness.

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P343 Evaluation of the age-related reference values of aortic pulse wave velocity in healthy subjects using Doppler echocardiography

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez319.196 ◽

2020 ◽

Vol 21 (Supplement_1) ◽

Author(s):

G Styczynski ◽

K Cienszkowska ◽

M Ludwiczak ◽

C Szmigielski

Keyword(s):

Pulse Wave Velocity ◽

Wave Velocity ◽

Transit Time ◽

Reference Values ◽

Doppler Echocardiography ◽

Healthy Subjects ◽

Aortic Stiffness ◽

Pulse Wave ◽

Aortic Pulse Wave Velocity ◽

Age Related

Abstract Introduction Aortic pulse wave velocity (aPWV) is a measure of aortic stiffness, which is an indicator of vascular aging and has established independent prognostic role in predicting cardiovascular complications. aPWV can be measured with various non-invasive methods, but with different reference values depending on the technique used. The Doppler echocardiography method is potentially widely accessible and has been recently showed to have high correlation with invasive reference method of aPWV based on intraarterial pressure evaluation. Purpose The aim of the study was to establish reference values of aPWV, measured by Doppler method during a standard echocardiography in healthy subjects. Methods 121 healthy adults, normotensive, non-smoking, without chronic diseases and not taking medication, were included. All the patients were divided into 5 groups due to age criterion (D1-age 21-30 yrs., n = 33; D2-age 31-40 yrs., n= 23; D3-age 41-50 yrs., n = 26; D4-age 51-60 yrs., n = 22; and D5-age 61-70 yrs., n = 17). During a routine echocardiographic examination with a cardiac probe, standard echocardiographic and anthropometric parameters were acquired. Additionally, 10 Doppler waveforms were recorded in the distal aortic arch and then in the left external iliac artery. The transit time was calculated as a difference between time delay of the two points of the Doppler recordings relative to ECG signal. The distance between proximal and distal points was measured over the body surface using a flexible measuring tape. aPWV values were calculated according to the formula: PWV = distance/transit time. Results The mean age of the studied group was 42 ± 13 yrs., BMI 24.5 ± 3.4, SBP 123 ± 10.39 mm Hg, DBP 76.98 ± 6.53 mm Hg, HR 64 ± 10 bpm. aPWV 5.28 ± 1.07; LVEDD 4.6 ± 0.4 cm; LA 3.65 ± 0.33 cm; aorta 3.26 ± 0.38 cm; LVMI 87.12 ± 15.00 g/m2. In the studied subjects, aPWV did not differ according to sex (females, n = 53, aPWV 5.38 ± 1.21 m/s vs. males, n = 68, aPWV 5.21 ± 0.94 m/s, p = 0.37). In the multivariate linear regression analysis only age and SBP were independently associated with aPWV, but none of the echocardiographic parameters studied. Mean aPWV values with 95% confidence interval (95%CI) for each decade of life were recorded as follows: D1-age 21-30, aPWV 4.56 m/s (95%CI 4.41 to 4.72), D2-age 31-40, aPWV 4.65 m/s (95%CI 4.37 to 4.94), D3-age 41-50, aPWV 5.15 m/s (95%CI 4.88 to 5.43), D4-age 51-60, aPWV 5.96 m/s (95%CI 5.54 to 6.38), D5-age 61-70, aPWV 6.88 m/s (95%CI 6.42 to 7.34). Conclusions We report age-related values of aPWV in a healthy population measured by Doppler echocardiography method. This may be helpful in future research exploring the associations between aortic stiffness, cardiac function and cardiovascular prognosis in a large population of patients referred for echocardiography.

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