Large Artery Stiffness Research Articles

Cardiac-Related Pulsatility in the Insula Is Directly Associated With Middle Cerebral Artery Pulsatility Index.

Arterial stiffness in large arteries is a risk factor for cerebral small vessel disease and neurodegeneration. The challenge of accessing intracranial pulsatility noninvasively is one reason few studies provide empirical insight on the relationship between large artery and tissue pulsatility in the human brain. To investigate the association between the functional magnetic resonance imaging (fMRI)-derived cardiac-related pulsatility in the insular cortex and the ultrasound-derived pulsatility index in the middle cerebral artery (MCA-PI). Cross-sectional. Younger adults (11; 25 ± 4 years) and older adults with and without cardiovascular risk factors (44; 70 ± 6 years). T1 -weighted, fluid attenuated inversion recovery, and T2 *-weighted blood oxygenation level-dependent (BOLD) sequences at 3T. MCA-PI and cardiac-related pulsatility were assessed at rest by transcranial Doppler ultrasound and BOLD fMRI, respectively. Multivariate analyses of covariance between MCA-PI and cardiac-related pulsatility. Analysis of variance was used to assess regional differences. MCA-PI was associated with cardiac-related insular pulsatility (P = 0.037), but not whole-brain pulsatility (P = 0.81). Left insular pulsatility was higher than right insular pulsatility (P < 0.01) and was associated with diastolic blood pressure (P = 0.028). We show a correlation between ultrasound and fMRI measures of cerebrovascular pulsatility. This association provides insight into the transmission of pulsatile energy from large basal arteries at the Circle of Willis to downstream cerebrovascular beds and has implications for the utility of cardiac-related pulsatility as a potential marker for cerebral small vessel disease. 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:1454-1462.

4095Exercise and vascular ageing: a cross-sectional and randomized controlled trial

Abstract Background Vascular ageing can be quantified at subclinical stages by use of sensitive vascular biomarkers of the macro- and microcirculation. Detection of vascular impairments enables initiation of timely treatment strategies to counteract development of CV disease and improve CV outcome. Purpose To (a) compare large artery stiffness and retinal microvascular diameters in healthy life-long active and healthy sedentary older adults with CV risk patients, and (b) to assess the effects of short-term high-intensity exercise training on vascular health in these patients. Methods Seven hundred and eighty-three participants were screened for their CV risk and physical activity profile. We included 38 healthy active (HA, mean age 60±7 years) and 36 healthy sedentary (HS, mean age 60±7 years) as well as 84 sedentary patients with ≥2 CV risk factors (SR, mean age 59±6 years) in the cross-sectional approach. SR were randomized to a 12-week high-intensity interval training (HIIT) or physical activity recommendations after the baseline assessment. Carotid-femoral PWV (cfPWV) was measured as a marker of large artery stiffness and the central retinal arteriolar (CRAE) and venular (CRVE) diameters as well as the retinal arteriolar-to-venular diameter ratio (AVR) were measured as a marker of the microcirculation. Standard procedures of anthropometric measurements were implemented. Results Anthropometric parameters differed between the groups according to the inclusion criteria. cfPWV was highest in SR (8.2±1.4m/s) compared to HS (7.5±1.6m/s) and HA (7.0±1.1 m/s). HA had a lower cfPWV compared to HS (p&lt;0.05) and SR (p&lt;0.001). HA had wider CRAE (179±14μm) and narrower CRVE (204±17μm) compared to HS (CRAE: 172±11 μm; CRVE: 209±11 μm) resulting in a higher AVR in HA (0.88±0.05) compared to HS (0.83±0.04, p&lt;0.001). By contrast, SR showed narrower CRAE (171±14 μm) and wider CRVE (218±16μm, p&lt;0.05) compared to HS resulting in a lower AVR (0.79±0.05, p&lt;0.001) compared to HS and HA. HIIT in SR improved most classic CV risk factors. Additionally, CRAE increased (pre: 175±14μm vs post: 181±13μm, p=0.001) and CRVE decreased (pre: 222±14μm vs post: 220±14μm, p=0.007) in the HIIT group without changes in the cfPWV. PWV was significantly but moderately associated with AVR (r=−0.2, p=0.01). Conclusions Life-long physical activity and fitness were associated with lower arterial stiffness and favourable retinal vessel diameters in healthy individuals. CV patients had higher arterial stiffness and lower AVR. Short-term HIIT improved retinal microvascular phenotype without changes in large artery stiffness. Retinal vessel diameters are sensitive diagnostic tool for CV risk stratification and subclinical vascular disease monitoring in CV patients. Short-term HIIT may postpone development of small vessel disease in older patients. Acknowledgement/Funding Swiss National Science Foundation, Nora van Meeuwen-Häfliger Stiftung

P3834PULSE-COR REGISTRY: non invasive LV stiffness assessment in subjects with essential hypertension

Abstract Background Left ventricle (LV) diastolic dysfunction for a long time had been associated with its hypertrophy. But recent studies have demonstrated that it is more associated with LV fibrosis which is also the cause of poor prognosis. Unfortunately, there is no proven tool for its clinicall assessment. The aim of the study was to demonstrate which of LV stiffness parameters are associated with arterial stiffness which we can measure using validated techniques. Methods PULSE-COR is one center registry started in 2011 and still running. We included 779 subjects with AH. Final analysis included 320 patients that underwent all necessary diagnostic procedures from whom we have identified a separate cohort of patients (n=283) with essential AH without any significant comorbidities. We used SphygmoCor device (AtCor, Australia) for the determination carotid-femoral pulse wave velocity (cfPWV). Also we measured CAVI and ankle-brachial index (ABI) with the mean of VaSera 1500 (Fukuda Denshi, Japan). Ultrasound diagnostics included vascular ultrasound with intima-media thickness (IMT) measurement. Echocardiography was done according ASE standardized protocol, LV diastolic function was evaluated according to ASE 2016 guidelines. Ventricle-arterial coupling (VAC) was evaluated using standardized formula. In order to find associations we used Spearman correlation analysis. Results Mean age was 53,6±2,0 years, 17 men and 30 women. Mean body mass index 29,8±1,0 m/kg2, mean systolic blood pressure (SBP) was 159,8±4,5 mmHg, diastolic BP (DBP) was 97,9±2,6 mmHg, pulse BP (PBP) was 62,0±3,5 mmHg and heart rate (HR) was 76,6±2,2 bits per min. VAC was significantly associated with both (left and right) CAVI (R=0,698; P=0,012 and R=0,683; P=0,014, respectively). ABI was significantly associated with both E/A and E/e' (R=0,716; P=0,006 and R=0,764; P=0,002, respectively). Ea was significantly associated with IMT (R=0,491; P=0,24), total cholesterol (R=0,499; P=0,07), low-density lipoproteins (R=0,687; P=0,001), cfPWV was associated with almost the same factors (R=0,248; P=0,001 for correlation with IMT, R=0,382; P=0,01 for correlation with low-density lipoproteins). Ees was significantly associated with E/A (R=0,159; P=0,007); E/e' (R=-0,130; P=0,029), end diastolic volume (R=0,644; P&lt;0,001) and with blood lymphocytes (R=-0,678; P=0,001). Conclusions We have found that VAC was significantly associated with arterial elasticity (CAVI), but we have not any correlation with CAVI for none of its component (Ea or Ees). Arterial elastance (Ea) was associated with similar factors as large arteries stiffness (cfPWV). Ventricle elastance instead was associated with diastolic dysfunction. All these components play role in clinical LV stiffness assessment.

P2640The effect of dry-weight reduction guided by lung ultrasound on ambulatory aortic blood pressure and arterial stiffness parameters in hemodialysis patients

Abstract Introduction and purpose Arterial stiffness and aortic blood pressure (BP) augmentation are significantly increased in hemodialysis patients. Recent studies suggest that the prognostic significance of ambulatory recordings of arterial stiffness is high in hemodialysis. This study examines for the first time the effect of dry weight reduction with a standardized lung-ultrasound-guided strategy on ambulatory aortic BP and arterial stiffness parameters in hypertensive hemodialysis patients. Methods A total 71 hemodialysis patients with hypertension (mean home BP ≥135/85 mmHg), that were clinically euvolemic, were included in this single-blind randomized clinical trial. Patients were randomized in a 1:1 ratio in the active group (n=35), following a strategy for dry-weight reduction guided by the total number of US-B lines (US-B lines score) prior to a mid-week dialysis session and the control group (n=), following standard-of-care treatment. All patients underwent 48-hour ABPM with the Mobil-O-Graph monitor (IEM, Stolberg, Germany) and PWV measurement in office with SphygmoCor (ArtCor, Sydney, Australia) at baseline and after 8-weeks. Results Overall, the US-B lines change during follow-up were −5.3±12.5 in active versus +2.2±7.6 in control group (p&lt;0.001), which corresponded to dry-weight changes of −0.71±1.39 versus +0.51±0.98 kg (p&lt;0.001). The change in 48-hour cSBP was significantly greater in the active group (−6.30±8.90 vs −0.50±12.46, p=0.027); the relevant cDBP fall was marginally greater (−3.85±6.61 vs −0.63±8.36, p=0.077) in the active group. 48-hour cPP (41.51±9.63 vs 39.06±9.61 mmHg, p=0.004) and 48-hour PWV (9.30±2.00 vs 9.08±2.04 m/sec, p=0.032) were significantly reduced from baseline to study-end in the active group but remained unchanged in controls. In contrast, 48-hour AIx and AIx(75) did not change between baseline and study-end in both groups; changes in AIx(75) were similar in the two groups (−0.97±3.51 vs −0.36±4.25, p=0.517). PWV measured in office was decreased from baseline to study-end in the active (10.07±2.66 vs 9.79±2.81, p=0.038) but not in the control group. Conclusions A lung-ultrasound-guided strategy for dry-weight reduction reduces ambulatory aortic BP and ambulatory or office PWV, but not ambulatory AIx(75). These results suggest that dry-weight reduction can primarily reduce aortic BP levels and large arteries stiffness but not wave reflections from the periphery.

Abstract 149: Postpartum Cognitive Function in Young Women With a History of Preeclampsia: Association With Blood Pressure but Not Large Artery Stiffness

Introduction: Women with a history of preeclampsia (PE) have elevated large artery stiffness and blood pressure (BP) several years postpartum. Age-related increases in aortic stiffness are deleterious to brain structure and cognitive function; however, the relationship between large artery stiffness and cognitive function has not been assessed in women with a history of PE. The purpose of this study was to determine the extent to which large artery stiffness and BP are associated with cognitive function in women with a history of PE. Methods: Women with a history of PE (n=12; age 33±1 yrs; BMI 28.5±3.1 kg/m 2 ) and healthy pregnancy controls (n=7; age 34±2 yrs; BMI 26.5±4.0 kg/m 2 ) were assessed one year postpartum. Brachial BP was collected in triplicate using an automated cuff. Aortic stiffness was measured via applanation tonometry and quantified as carotid-femoral pulse wave velocity (cfPWV). Carotid stiffness (β-stiffness) was obtained via ultrasonography and carotid tonometry. Cognitive function was assessed in domains of memory, processing speed, and executive function. Results: Women with a history of PE had higher systolic BP (121±4 vs. 104±3 mmHg, p&lt;0.01) and cfPWV (6.2±0.4 vs. 5.1±0.2 m/s, p=0.06), though the latter did not reach statistical significance. There was no difference between groups in β-stiffness (6.1±0.4 vs. 6.1±0.6 U, p=0.97). Cognitive domains of executive function, memory, and processing speed did not differ between groups (all p&gt;0.05). Systolic BP was associated with reductions in executive function (r = -0.52, p=0.04) independent of education level, but was not related to reductions in memory or processing speed. Arterial stiffness was not associated with cognition. Conclusions: Women with a history of PE had elevated systolic BP and aortic stiffness, but only BP was associated with reductions in executive function. These preliminary findings suggest that young women with a history of PE may be vulnerable to reductions in cognitive function related to persistent elevated systolic BP.

Abstract P1117: Dissimilarities Between and Carotid and Forearm Pressure-Decay and Windkessel Parameters: Implications for Circulatory Models

We studied whether: 1) the carotid and forearm diastolic pressure-decay time constants (tau) are similar and 2) the associated Windkessel (WK)-derived compliance and stiffness values are also similar and are related to arterial stiffness. Ambulatory normotensive and hypertensive subjects were studied after 30 minutes of supine rest with radial and carotid arterial tonometry (Sphygmocor), standard oscillometric cuff BP, and central (heart-femoral, hf) and peripheral (femoral-ankle, fa) pulse wave velocity (PWV, Colin VP1000). Brachial and carotid Doppler flow studies were performed in a subset. Tonograms were photo-digitized and the pressure in late diastole was modeled as an exponential decay to an asymptote A with time constant tau and start-decay time t0. [Resistance = mean pressure/flow; WK compliance = tau/resistance and WK stiffness = 1/WK compliance.] Tonometry and PWV data were available in 98 individuals; carotid and forearm blood flow in 22: (mean[SD]) age 50[20] years, weight 81[17] kg, BP 134/77[17/12] mmHg, resting HR 66[12], 38% female. Data are presented in the Table; hfPWV and faPWV were well correlated (p&lt;0.001) but neither was correlated with carotid or forearm tau or the corresponding regional WK stiffness. We conclude that diastolic pressure decay (tau) and WK stiffness (or compliance) are not systemic indicators but rather unique regional characteristics not related to central or peripheral large artery stiffness. These findings suggest that single-WK models do not adequately represent the arterial circulation.

Aortic Augmentation Index is Dependent on Bodyside in Healthy Young Subjects

Aortic augmentation index (AIx) is a commonly used measure to evaluate the arterial stiffness of large elastic arteries. It has been used as an indicator for cardiovascular risk in clinical practice. To evaluate the difference in the aortic AIx assessed from the left and the right hand in a group of healthy young adults using SphygmoCor and Arteriograph devices. 32 subjects were enrolled in this study (27 ± 7years), 16 male and 16 female volunteers participated. Equally, half of the gender groups were left-handed and another half right-handed. It was found that the aortic AIx values assessed from the pressure waveforms of the right and the left hand are different and significantly higher in the left hand. Using a SphygmoCor device, the mean difference between the aortic AIx values from the right and the left hand among the whole study group was found - 4.78 ± 4.31% and using an Arteriograph the aortic AIx values were - 3.92 ± 3.90%. Aortic AIx values assessed from the right and the left hand were linearly related to each other for both devices. Moreover, it was found that the values of the aortic. AIx are independent of the subject's handedness. It has to be pointed out that subjects who cannot be subjected to assessment of the aortic AIx from one side of the body could have different AIx values estimated from the recorded pressure waveform from the other bodyside.

Frequent nocturnal urination in older men is associated with arterial stiffness: The Nagahama study.

Nocturia in older adults has been reported to be a risk factor for cardiovascular outcomes, and the stiffening of large arteries might be an underlying mechanism. To clarify the possible association between nocturia and arterial stiffness, we analyzed a dataset from the Japanese general population. Study participants consisted of 5928 community residents (mean age: 60.0 ± 11.8 years). The frequency of nocturnal urination was recorded for 1 week using a sleep diary. Arterial stiffness was assessed by brachial-to-ankle pulse wave velocity (baPWV). Sleep blood pressure was measured automatically at 0000, 0200, and 0400 hours by wearing a cuff on the upper arm during sleep. The mean baPWV was 1278 ± 227 cm/s. The frequency of nocturnal urination showed a linear positive association with baPWV (P < 0.001). The association between a sleep diary-based nocturnal urination frequency > 1.5 times/night (corresponding to a ≥ 2 times/night frequency obtained by the questionnaire) and baPWV remained significant after adjusting for major covariates, including office blood pressure (β = 0.051, P < 0.001) and sleep blood pressure (β = 0.040, P < 0.001). This association was more prominent in men (β = 0.069, P < 0.001) than in women (β = 0.023, P = 0.013), particularly in older (β = 0.068, P = 0.006) compared with younger (β = 0.029, P = 0.270) men. Frequent nocturnal urination was independently associated with baPWV in older men. Nocturia may be a marker for cardiovascular disease risks that cannot be assessed by conventional risk factors such as blood pressure.

Inflammation as a mediator of arterial ageing.

What is the topic of this review? This review summarizes and synthesizes what is known about the contribution of inflammation to age-related arterial dysfunction. What advances does it highlight? This review details observational evidence for the relationship of age-related inflammation and arterial dysfunction, insight from autoimmune inflammatory diseases and their effects on arterial function, interventional evidence linking inflammation and age-related arterial dysfunction, insight into age-related arterial inflammation from preclinical models and interventions to ameliorate age-related inflammation and arterial dysfunction. Advanced age is a primary risk factor for cardiovascular disease, the leading cause of death in the industrialized world. Two major components of arterial ageing are stiffening of the large arteries and impaired endothelium-dependent dilatation in multiple vascular beds. These two alterations are major contributors to the development of overt cardiovascular disease. Increasing inflammation with advanced age is likely to play a role in this arterial dysfunction. The purpose of this review is to synthesize what is known about inflammation and its relationship to age-related arterial dysfunction. This review discusses both the initial observational evidence for the relationship of age-related inflammation and arterial dysfunction and the evidence that inflammatory autoimmune diseases are associated with a premature arterial ageing phenotype. We next discuss interventional and mechanistic evidence linking inflammation and age-related arterial dysfunction in older adults. We also attempt to summarize the relevant evidence from preclinical models. Lastly, we discuss interventions in both humans and animals that have been shown to ameliorate age-related arterial inflammation and dysfunction. The available evidence provides a strong basis for the role of inflammation in both large artery stiffening and impairment of endothelium-dependent dilatation; however, the specific inflammatory mediators, the initiating factors and the relative importance of the endothelium, smooth muscle cells, perivascular adipose tissue and immune cells in arterial inflammation are not well understood. With the expansion of the ageing population, ameliorating age-related arterial inflammation represents an important potential strategy for preserving vascular health in the elderly.

Wave reflections and systemic vascular resistance are stronger determinants of pulse pressure amplification than aortic stiffness in drug-naïve hypertensives

ABSTRACTBackground: Aortic-to-brachial pulse pressure (PP) amplification is a novel biomarker that prognosticates the cardiovascular risk above and beyond central aortic and brachial blood pressure. This phenomenon is modulated by left ventricular contractility and chronotrophy, large-artery stiffness and reflecting properties of microcirculation. However, the relative importance of these parameters as hemodynamic determinant of PP amplification remains elusive.Methods: A total of 88 consecutive drug-naïve hypertensives underwent a non-invasive assessment of central and peripheral hemodynamics via impedance cardiography and pulse wave analysis. Participants were classified into tertiles according to the magnitude of PP amplification. Hemodynamic determinants of low PP amplification were explored in univariate and multivariate regression analysis.Results: Compared with the high tertile, patients within the low PP amplification tertile were older and more commonly female and had lower height, weight and heart rate. Augmentation index (AIx) and systemic vascular resistance index (SVRI) were higher among patients within the low PP amplification tertile, whereas aortic pulse wave velocity (PWV) did not differ among groups. In multivariate analysis, higher AIx (OR: 1.27; 95% CI: 1.09–1.48) and higher SVRI were independently associated with higher odds for low PP amplification, whereas higher heart rate was the only parameter related to lower odds for low PP amplification (OR: 0.84; 95% CI: 0.71–0.99).Conclusion: This study shows that among newly-diagnosed drug-naïve hypertensives, elevated wave reflections and systemic vascular resistance are stronger determinants of PP amplification than aortic stiffness.

Cardio-ankle Vascular Index As A Non-invasive Screening Tool For Cardio-vascular Disease In Youth

Introduction: Risk factors associated with the development of cardiovascular disease, including hypertension, dyslipidemias, and obesity, are becoming increasingly prevalent in children and adolescents. Therefore, noninvasive methods of assessing atherosclerotic risk in youth need to be developed and standardized. Cardio-ankle vascular index (CAVI) reflects the stiffness of large and small conduit arteries and is independent of blood …

Retraction: Stiffening-Induced High Pulsatility Flow Activates Endothelial Inflammation via a TLR2/NF-κB Pathway.

Stiffening of large arteries is increasingly used as an independent predictor of risk and therapeutic outcome for small artery dysfunction in many diseases including pulmonary hypertension. The molecular mechanisms mediating downstream vascular cell responses to large artery stiffening remain unclear. We hypothesize that high pulsatility flow, induced by large artery stiffening, causes inflammatory responses in downstream pulmonary artery endothelial cells (PAECs) through toll-like receptor (TLR) pathways. To recapitulate the stiffening effect of large pulmonary arteries that occurs in pulmonary hypertension, ultrathin silicone tubes of variable mechanical stiffness were formulated and were placed in a flow circulatory system. These tubes modulated the simulated cardiac output into pulsatile flows with different pulsatility indices, 0.5 (normal) or 1.5 (high). PAECs placed downstream of the tubes were evaluated for their expression of proinflammatory molecules (ICAM-1, VCAM-1, E-selectin and MCP-1), TLR receptors and intracellular NF-κB following flow exposure. Results showed that compared to flow with normal pulsatility, high pulsatility flow induced proinflammatory responses in PAECs, enhanced TLR2 expression but not TLR4, and caused NF-κB activation. Pharmacologic (OxPAPC) and siRNA inhibition of TLR2 attenuated high pulsatility flow-induced pro-inflammatory responses and NF-κB activation in PAECs. We also observed that PAECs isolated from small pulmonary arteries of hypertensive animals exhibiting proximal vascular stiffening demonstrated a durable ex-vivo proinflammatory phenotype (increased TLR2, TLR4 and MCP-1 expression). Intralobar PAECs isolated from vessels of IPAH patients also showed increased TLR2. In conclusion, this study demonstrates for the first time that TLR2/NF-κB signaling mediates endothelial inflammation under high pulsatility flow caused by upstream stiffening, but the role of TLR4 in flow pulsatility-mediated endothelial mechanotransduction remains unclear.

PULSE-COR REGISTRY

Objective: The aim of current analysis was to evaluate association of different factors with arterial stiffness and LV stiffness in patients only with essential arterial hypertension (AH). Design and method: PULSE-COR is one center registry started in 2011 and still running. We included 779 (50%) were subjects with AH. Final analysis included 320 patients that underwent all necessary diagnostic procedures from whom we have identified a separate cohort of patients (n = 283) with essential AH without any significant comorbidities. We measured carotid-femoral pulse wave velocity (cfPWV), CAVI and ankle-brachial index (ABI) by of VaSera 1500 (Fukuda Denshi, Japan), intima-media thickness (IMT) measurement, made standard echocardiography with ventricle-arterial coupling (VAC). In order to find associations we used Spearman correlation analysis. Results: Mean age was 53,6 ± 2,0 years, 17 men and 30 women. Mean body mass index 29,8 ± 1,0 m/kg2, mean systolic blood pressure (SBP) was 159,8 ± 4,5 mmHg, diastolic BP (DBP) was 97,9 ± 2,6 mmHg, pulse BP (PBP) was 62,0 ± 3,5 mmHg and heart rate (HR) was 76,6 ± 2,2 bits per min. VAC was significantly associated with both (left and right) CAVI (R = 0,698; P = 0,012 and R = 0,683; P = 0,014, respectively). ABI was significantly associated with both E/A and E/e′ (R = 0,716; P = 0,006 and R = 0,764; P = 0,002, respectively). Ea was significantly associated with IMT (R = 0,491; P = 0,24), total cholesterol (R = 0,499; P = 0,07), low-density lipoproteins (R = 0,687; P = 0,001), cfPWV was associated with almost the same factors (R = 0,248; P = 0,001 for correlation with IMT, R = 0,382; P = 0,01 for correlation with low-density lipoproteins). Ees was significantly associated with E/A (R = 0,159; P = 0,007); E/e′ (R = −0,130; P = 0,029), end diastolic volume (R = 0,644; P < 0,001). Conclusions: We have found that VAC was significantly associated with arterial elasticity (CAVI), but we have not any correlation with CAVI for none of its component (Ea or Ees). Arterial elastance (Ea) was associated with similar factors as large arteries stiffness (cfPWV). Ventricle elastance instead was associated with diastolic dysfunction.

CALCULATION OF ARTERIAL PATH LENGTH FOR CAROTID-FEMORAL PULSE WAVE VELOCITY DETERMINATION USING AN ESTABLISHED FORMULA

Objective: Despite being established as the gold standard for quantifying large artery stiffness and its additive value beyond traditional risk factors in the prognosis of hypertension, carotid-femoral pulse wave velocity (cfPWV) is not recommended for routine clinical practice in the current guidelines due, in part, to practical limitations with its measurement. A formula was recently developed (Weir-McCall et al. Hypertension. 2018;71 (5):937–945) for calculation of both left- and right-side arterial path length for cfPWV determination using routinely collected clinical parameters (gender, age, weight, height, heart rate, diastolic blood pressure). However, only the right-side formula was validated. This study aimed to determine the validity of the left-side formula and whether accounting for side of cfPWV measurement would improve the agreement between formula-calculated and measured cfPWV. Design and method: Arterial path length was re-calculated in 127 subjects (aged 65 ± 12 years, 51 females) using the left- (n = 71) and right-side (n = 56) formula according to the side on which their cfPWV was previously measured. The formula-calculated distances were then used to re-calculate cfPWV. Arterial path length and cfPWV were also re-calculated in all 127 subjects using only either the left- or right-side formula. Results: Mean differences between formula-calculated and measured arterial path length and cfPWV were 29.5 ± 42.5 mm (mean ± SD, P < 0.001), 0.03 ± 1.0 m/s (P = 0.775) and 5.1 ± 35.4 mm (P = 0.286), 0.8 ± 0.7 m/s (P < 0.001) for left- and right-side, respectively, giving an average difference of 18.7 ± 41.2 mm (P < 0.001), 0.4 ± 0.9 m/s (P < 0.001). When only the left-side arterial length formula was used, the mean differences were 34.2 ± 40.9 mm (P < 0.001), 0.7 ± 0.9 m/s (P < 0.001). When only the right arterial path length formula was used, the mean differences were −0.21 ± 39.6 mm (P = 0.953), 0.1 ± 0.9 m/s (P = 0.378). Conclusions: Whilst the left-side formula resulted in a larger bias in arterial path length compared with the right-side formula, the resulting cfPWV had a better agreement with measured values. On a sample population level, the best agreement was achieved when only the right-side formula was used. These findings demonstrate that if a formula for path length is used, the left-side and right-side formulae result in different ranges of cfPWV differences in individual measurements and in population studies.

PULSE WAVE VELOCITY AND CIRCADIAN VARIABILITY IN WELL CONTROLLED HYPERTENSIVE PATIENTS

Objective: Pulse wave velocity (PWV) is the gold standard for measuring large artery stiffness. A PWV >10m/s is considered a conservative estimate of significant alterations of aortic function in middle-aged hypertensive patients. Although commonly used, there are only a few reports investigating the 24-hour variability in PWV measurements, the determination of which is important when using PWV as a clinical marker of target organ damage. The aim of this study was to investigate the variability in PWV measurements and factors that may influence PWV variability during 24 hours. Design and method: A prospective study was conducted in 55 well controlled hypertensive patients (mean age 65.8 ± 11.8 years) and 21 healthy control subjects (mean age 55.6 ± 18.9 years). In all subjects, complete blood chemistry (including SUA determination), echocardiographic examination, office and 24 h ambulatory blood pressure (BP) as well as 24 h ambulatory PWV and central (BP) measurement were performed Results: 24 hours systolic BP, central BP and PWV (p < 0.001) were significantly higher in hypertensive patients in confront to health subjects, but not diastolic BP (p = 0.140) levels. Specifically, the mean of PWV, SBP and cBP during 24 h was 9.7 (±0.3) vs 7.7 (± 0.3); 131.6 (±4.6) vs 122.8 (±5.9) and 137.7 (±4.3) vs 125.6 (± 4.2) for hypertensives and controls respectively. However, the mean of DBP during 24 h was 78.7 (±4.1) for patients and 79.4 (±5.6) for controls. Moreover, PWV of patients was significantly correlated with SBP, DBP (r = 0.411) and cBP (r = 0.717) levels (p < 0.001). Significant correlations were found between PWV of controls and SBP (r = 0.616), DBP (r = 0.499) and cBP (r = 0.579) levels (p < 0.001). PWV levels presented a small variability during the whole 24 hours (±0,3) suggesting that measurement and reproducibility of this marker are not influenced by a circadian rhythm. Conclusions: PWV assessment may be performed any time during 24 hours in an outpatient clinic. In our study, we didn’t find a circadian variability that may influence the reproducibility of PWV.

Retinal vessel reactivity is not attenuated in patients with type 2 diabetes compared with matched controls and is associated with peripheral endothelial function in controls

Background and aimsAttenuated retinal vasoreactivity in patients with type 2 diabetes preceding diabetic retinopathy development has been proposed to reflect local endothelial dysfunction.Whether retinal vessel reactivity is associated with peripheral endothelial dysfunction and large artery stiffness in patients with type 2 diabetes remains to be elucidated. MethodsTwenty patients with type 2 diabetes without retinopathy and 20 sex- and age matched controls (diabetes duration: 9.9 years (range 6.0;12.4), 40% male, age: 66.5 ± 7.3 (diabetes) and 65.2 ± 7.6 years (controls)) were included. Endothelial function was assessed using EndoPAT. Arterial stiffness was assessed by carotid-femoral pulse wave velocity using the SphygmoCor. Retinal blood supply regulation was examined by retinal arteriolar diameter change during 1) isometric exercise (hand-weight lifting), 2) exposure to flickering lights, and 3) a combined stimulus of 1) + 2) using the Dynamic Vessel Analyzer. ResultsNo significant differences were observed in retinal vessel reactivity in T2DM patients compared to controls. Endothelial function was associated with mean arteriolar diameter change during only the combination intervention, (Beta = 0.033 [0.0013;0.064], p = 0.042) in the overall population of patients and controls. When groups were analyzed separately, the associations was statistically significant only in controls. However, formal test for interaction was not statistically significant, p = 0.40. No association was observed between pulse wave velocity and retinal arteriolar %-diameter change in patients or controls. ConclusionPeripheral endothelial function was associated with retinal arteriolar diameter change in the combined sample. The association seemed to be driven primarily by the controls. Our findings indicate that peripheral endothelial function is reflective of endothelial function in the retina mainly in subjects without T2DM, whereas an association in T2DM without retinopathy was not observed. Further studies are needed in T2DM patients with more advanced retinopathy.

Individual and Neighborhood Deprivation and Carotid Stiffness.

Large artery stiffness is an index of vascular aging associated with cardiovascular mortality. Whereas traditional risk factors for arterial stiffness are known, the contribution of socioeconomic factors is less reported. We sought to determine the relationship between arterial stiffness and socioeconomic deprivation (at the individual and neighborhood levels) in healthy males and females. In 7803 adults, carotid stiffness was determined by high-precision carotid echo-tracking. Individual deprivation data included education, living alone, occupation, and Evaluation of the Deprivation and Inequalities of Health in Healthcare Centers score. Neighborhood deprivation was determined from commune level data (smallest administrative subdivision) available from French National Institute of Statistics and Economic Studies (2011) using principal component analysis. The separate and combined associations between individual and neighborhood deprivation (main exposures) and carotid stiffness (outcome) were quantified using linear and multilevel model adjusted for traditional risk factors. Analyses were conducted separately in males and females. Individual deprivation (lower education and occupation in males and living alone and higher Evaluation of the Deprivation and Inequalities of Health in Healthcare Centers in both populations) was adversely related to carotid stiffness, independently of potential confounders ( P<0.05). Neighborhood deprivation was adversely related to carotid stiffness in males ( P<0.05), but not in females. Socioeconomic deprivation, both at individual and, to a lesser extent, neighborhood level are associated with carotid stiffness in males. Only individual deprivation is associated with carotid stiffness in females.

Increased carotid stiffness and remodelling at early stages of chronic kidney disease.

Increased carotid stiffness and remodelling is reported in patients with moderate and advanced chronic kidney disease (CKD) and is associated with cardiovascular events. Here, we tested the hypothesis that carotid artery alterations start earlier, during mild CKD. Within the Paris Prospective Study 3, a large prospective observational survey of nonreferred people aged 50-75 who received an extensive health check-up, there were 294 participants with glomerular filtration rate (GFR) of at least 45 and less than 60 ml/min per 1.73 m (Stage 3A CKD), 840 participants with GFR 60-89 ml/min per 1.73 m with proteinuria (Stage 2 CKD), 4666 participants with GFR 60-89 ml/min per 1.73 m without proteinuria and 3317 individuals with GFR at least 90 ml/min per 1.73 m at study recruitment. Carotid artery measurements were performed using a high-resolution echotracking device. Compared with patients with GFR at least 90 ml/min per 1.73 m, the carotid distensibility and strain progressively decreased (P for trend <0.0001), whereas carotid stiffness progressively increased (P for trend <0.0001) across GFR categories starting at early stage from GFR 60-89 ml/min per 1.73 m without proteinuria. Higher Young's elastic modulus was observed only for Stage 3A CKD, whereas carotid internal diastolic diameter did not differ between groups. The large arterial stiffening starts early during CKD, even in participants with a very mild reduction in renal function.

Memory impairment in spontaneously hypertensive rats is associated with hippocampal hypoperfusion and hippocampal vascular dysfunction

We investigated the effect of chronic hypertension on hippocampal arterioles (HippAs) and hippocampal perfusion as underlying mechanisms of memory impairment, and how large artery stiffness relates to HippA remodeling. Using male spontaneously hypertensive rats (SHR) and normotensive Wistar rats (n = 12/group), long-term (LTM) and spatial memory were tested using object recognition and spontaneous alternation tasks. Hippocampal blood flow was measured via hydrogen clearance basally and during hypercapnia. Reactivity of isolated and pressurized HippAs to pressure and pharmacological activators and inhibitors was investigated. To determine large artery stiffness, distensibility and elastin content were measured in thoracic aorta. SHR had impaired LTM and spatial memory associated with decreased basal blood flow (68 ± 12 mL/100 g/min) vs. Wistar (111 ± 28 mL/100 g/min, p < 0.01) that increased during hypercapnia similarly between groups. Compared to Wistar, HippAs from SHR had increased tone at 60 mmHg (58 ± 9% vs. 37 ± 7%, p < 0.01), and decreased reactivity to small- and intermediate-conductance calcium-activated potassium (SK/IK) channel activation. HippAs in both groups were unaffected by NOS inhibition. Decreased elastin content correlated with increased stiffness in aorta of SHR that was associated with increased stiffness and hypertrophic remodeling of HippAs. Hippocampal vascular dysfunction during hypertension could potentiate memory deficits and may provide a therapeutic target to limit vascular cognitive impairment.

The Na+K+-ATPase Inhibitor Marinobufagenin and Early Cardiovascular Risk in Humans: a Review of Recent Evidence.

This review synthesizes recent findings in humans pertaining to the relationships between marinobufagenin (MBG), a steroidal Na+/K+-ATPase inhibitor and salt-sensitivity biomarker, and early cardiovascular risk markers. Twenty-four-hour urinary MBG strongly associates with habitual salt intake in young healthy adults (aged 20-30years). Furthermore, in young healthy adults free of detected cardiovascular disease, MBG associates with increased large artery stiffness and left ventricular mass independent of blood pressure. These findings in human studies corroborate mechanistic data from rat studies whereby stimulation of MBG by a high salt intake or MBG infusion increased vascular fibrosis and cardiac hypertrophy. Twenty-four-hour urinary MBG may be a potential biomarker of early cardiovascular risk. Adverse associations between MBG-which increases with salt consumption-and early cardiovascular risk markers support the global efforts to reduce population-wide salt intake in an effort to prevent and control the burden of non-communicable diseases.