Progression Of Aortic Stiffness Research Articles

Visit-to-visit HbA1c variability is associated with aortic stiffness progression in participants with type 2 diabetes

BackgroundGlycemic variability plays an important role in the development of cardiovascular disease (CVD). This study aims to determine whether long-term visit-to-visit glycemic variability is associated with aortic stiffness progression in participants with type 2 diabetes (T2D).MethodsProspective data were obtained from 2115 T2D participants in the National Metabolic Management Center (MMC) from June 2017 to December 2022. Two brachial-ankle pulse wave velocity (ba-PWV) measurements were performed to assess aortic stiffness over a mean follow-up period of 2.6 years. A multivariate latent class growth mixed model was applied to identify trajectories of blood glucose. Logistic regression models were used to determine the odds ratio (OR) for aortic stiffness associated with glycemic variability evaluated by the coefficient of variation (CV), variability independent of the mean (VIM), average real variability (ARV), and successive variation (SV) of blood glucose.ResultsFour distinct trajectories of glycated hemoglobin (HbA1c) or fasting blood glucose (FBG) were identified. In the U-shape class of HbA1c and FBG, the adjusted ORs were 2.17 and 1.21 for having increased/persistently high ba-PWV, respectively. Additionally, HbA1c variability (CV, VIM, SV) was significantly associated with aortic stiffness progression, with ORs ranging from 1.20 to 1.24. Cross-tabulation analysis indicated that the third tertile of the HbA1c mean and VIM conferred a 78% (95% confidence interval [CI] 1.23–2.58) higher odds of aortic stiffness progression. Sensitivity analysis demonstrated that the SD of HbA1c and the highest HbA1c variability score (HVS) were significantly associated with the adverse outcomes independent of the mean of HbA1c during the follow-up.ConclusionsLong-term visit-to-visit HbA1c variability was independently associated with aortic stiffness progression, suggesting that HbA1c variability was a strong predictor of subclinical atherosclerosis in T2D participants.

Relation of Pulse Wave Velocity to Contemporaneous and Historical Blood Pressure in Female Twins.

An association between blood pressure and aortic stiffness is well known, but ambiguity remains as to whether one precedes the other. This study aimed to investigate the association of aortic stiffness with contemporaneous versus historic blood pressure and direction of causality between aortic stiffening and hypertension in female twins. Aortic stiffness, measured by carotid-femoral pulse wave velocity (PWV), and mean arterial pressure (MAP) was recorded in 2037 female TwinsUK participants (mean age: 62.4±9.7 years) at a single time point. A subset of 947 participants had repeat PWV and MAP measures (mean interval 5.5±1.7 years) with additional historic MAP (mean interval 6.6±3.3 years before baseline). Cross-sectional multivariable linear regression analysis confirmed PWV significantly associated with age and MAP. In longitudinal analysis, annual progression of PWV was not associated with historic MAP (standardized beta coefficient [β]=-0.02, P=0.698), weakly associated with baseline MAP (β=0.09, P=0.049) but strongly associated with progression (from baseline to most recent measurement) of MAP (β= 0.26, P<0.001). Progression of MAP associated with both baseline and progression of PWV (β=0.13, P=0.003 and β=0.24, P<0.001, respectively). Progression of aortic stiffness associates more strongly with contemporaneous MAP compared with historic MAP. In contrast, progression of MAP is associated with prior arterial stiffness. These findings suggest a bidirectional relationship between arterial stiffness and blood pressure, and that lowering blood pressure may prevent a cycle of arterial stiffening and hypertension.

Abstract 13679: Arterial Stiffness and Carotid Intima-Media Thickness Progression Preceding Worsening Left Ventricular Hypertrophy and Diastolic Dysfunction in Youth: A Temporal Causal Longitudinal Study

Introduction: Left ventricular hypertrophy (LVH) is a marker of cardiovascular events and is driven by ventriculo-vascular interactions with stiffening arteries. But longitudinal relations of left ventricle with aorta is uncharacterized in youth. Hypothesis: Aortic stiffening, measured as change in carotid-femoral pulse wave velocity (cfPWV), and arterial thickening measured as change in carotid intima-media thickness (cIMT) each independently predicts and precedes changes in LVH indices even after adjustment for BP. Methods: From the Avon Longitudinal Study of Parents and Children, UK birth cohort, 1856 adolescents (1011 females) were assessed at mean age 17.7 years and followed for 7 years. Vicorder measured cfPWV and ultrasound measured cIMT were grouped in tertiles as low (reference), moderate, and high. Echocardiography measured cardiac abnormalities are left ventricular mass indexed for height 2.7 (LVMI 2.7 ) ≥51g/m 2.7 as LVH; relative wall thickness ≥44 as hiRWT; LV diastolic function E/A as ≥1.5 (LVDD); and LV filling pressure E/e’ ≥8 as hiLVFP. Data were analysed with generalized logit mixed-effect model and cross-lagged structural equation path model adjusting for cardiometabolic and lifestyle factors. Results: Over follow-up, LVH prevalence increased from 3.6% to 7.2% and LVDD from 11.1 to 16.3%. High cfPWV progression was associated with worsening LVH [Odds ratio 1.23 (1.13 - 1.35); p&lt;0.001] and worsening hiLVFP [1.14 (1.13 - 1.14); p&lt;0.0001]. Likewise, high cIMT progression was associated with worsening LVH [1.27 (1.26 - 1.27); p&lt;0.0001] and worsening hiLVFP [1.17 (1.07 - 1.28); p&lt;0.001]. Neither cfPWV nor cIMT progression was associated with worsening hiRWT nor LVDD. In cross-lagged models, higher baseline cfPWV was associated with future LVMI 2.7 (β=0.06, SE, 5.14, p=0.035), RWT, LVDF, and LVFP. However, baseline LVMI 2.7 , RWT, LVDF, and LVFP were not associated with follow-up cfPWV. Baseline cIMT was not associated with follow-up cardiac indices and vice versa . Conclusions: Youth aortic stiffness progression temporally preceded and may causally associate with worsening LVH and hiLVFP but not hiRWT. Mechanistic delineation of coupling in ventriculo-vascular remodeling and consequent physiologic dysfunction is warranted.

Basal Vascular Smooth Muscle Cell Tone in eNOS Knockout Mice Can Be Reversed by Cyclic Stretch and Is Independent of Age.

Introduction and Aims: Endothelial nitric oxide synthase (eNOS) knockout mice develop pronounced cardiovascular disease. In the present study, we describe the alterations in aortic physiology and biomechanics of eNOS knockout and C57Bl/6 control mice at 2–12 months of age, including a thorough physiological investigation of age and cyclic stretch-dependent VSMC contractility and aortic stiffness. Methods and Results: Peripheral blood pressure and aortic pulse wave velocity were measured in vivo, and aortic biomechanical studies and isometric contractions were investigated ex vivo. Age-dependent progression of aortic stiffness, peripheral hypertension, and aortic contractility in eNOS knockout mice was absent, attenuated, or similar to C57Bl/6 control mice. Voltage-gated calcium channel (VGCC)-dependent calcium influx inversely affected isometric contraction and aortic stiffening by α1-adrenergic stimulation in eNOS knockout mice. Baseline aortic stiffness was selectively reduced in eNOS knockout mice after ex vivo cyclic stretch exposure in an amplitude-dependent manner, which prompted us to investigate cyclic stretch dependent regulation of aortic contractility and stiffness. Aortic stiffness, both in baseline conditions and after activation of vascular smooth muscle cell (VSMC) contraction, was reduced with increasing cyclic stretch amplitude. This cyclic stretch dependency was attenuated with age, although aged eNOS knockout mice displayed better preservation of cyclic stretch-dependency compared to C57Bl/6 control mice. Store operated calcium entry-medicated aortic stiffening as induced by inhibiting sarcoplasmic reticulum calcium ATPase pumps with 10 µM CPA was most pronounced in the aorta of aged mice and at low cyclic stretch amplitude, but independent of eNOS. Basal aortic tonus and VSMC depolarization were highly dependent on eNOS, and were most pronounced at low cyclic stretch, with attenuation at increasing cyclic stretch amplitude. Conclusion: eNOS knockout mice display attenuated progression of arterial disease as compared to C57Bl/6 control mice. Basal VSMC tone in eNOS knockout mice could be reduced by ex vivo exposure to cyclic stretch through stretch-dependent regulation of cytosolic calcium. Both baseline and active aortic stiffness were highly dependent on cyclic stretch regulation, which was more pronounced in young versus aged mice. Other mediators of VSMC contraction and calcium handling were dependent on cyclic stretch mechanotransduction, but independent of eNOS.

Prognostic Value of Changes in Aortic Stiffness for Cardiovascular Outcomes and Mortality in Resistant Hypertension: a Cohort Study.

The prognostic importance of changes in aortic stiffness for the occurrence of adverse cardiovascular outcomes and mortality has never been investigated in patients with resistant hypertension. We aimed to evaluate it in a prospective cohort of 442 resistant hypertension individuals. Changes in aortic stiffness were assessed by 2 carotid-femoral pulse wave velocity (CF-PWV) measurements performed over a median time interval of 4.7 years. Multivariate Cox analysis examined the associations between changes in CF-PWV (evaluated as continuous variables and categorized into quartiles and as increased/persistently high or reduced/persistently low) and the occurrence of total cardiovascular events (CVEs), major adverse CVEs, and cardiovascular/all-cause mortalities. During a median follow-up of 4.1 years after the second CF-PWV measurement, there were 49 total CVEs (42 major adverse CVEs) and 53 all-cause deaths (32 cardiovascular). As continuous variables, increments in absolute and relative changes in CF-PWV were associated with higher risks of CVEs and major adverse CVEs occurrence, but not of mortality. Divided into quartiles of CF-PWV changes, risks increased in the third and fourth quartile subgroups in relation to the reference first quartile subgroup (those with greatest CF-PWV reductions) for all outcomes. Patients who either increased or persisted with high CF-PWV had excess risks of cardiovascular morbidity/mortality, with hazard ratios ranging from 2.7 to 3.0, in relation to those who reduced or persisted with low CF-PWV values. In conclusion, reducing or preventing progression of aortic stiffness was associated with significant cardiovascular protection in patients with resistant hypertension, suggesting that it may be an additional clinical target of antihypertensive treatment.

Diurnal pattern of salivary cortisol and progression of aortic stiffness: Longitudinal study

BackgroundThe positive direct relation between stress and the development of cardiovascular disease has increasingly been recognized. However, the link between hypothalamic-pituitary-adrenal (HPA) dysregulation and subclinical cardiovascular disease has not been studied longitudinally. We investigated the relation of diurnal salivary cortisol, as a biological marker of stress levels, with progression of aortic stiffness over five years. MethodsA total of 3281 people (mean age 65.5) in the Whitehall II prospective study provided six saliva samples on a single weekday. We assessed the diurnal salivary cortisol using the daytime slope and bedtime level. Aortic stiffness was measured by carotid-femoral pulse wave velocity (PWV) at baseline (2007–2009) and five years later (2012–2013). Linear mixed models were used to estimate the association of diurnal salivary cortisol with baseline PWV and five-year longitudinal changes. ResultsDiurnal salivary cortisol were not associated with PWV at baseline. Among women but not men, a 1-SD shallower salivary cortisol slope at baseline was associated with a five-year increase in PWV (β = 0.199; 95% CI = 0.040, 0.358 m/s) and higher bedtime cortisol level (β = 0.208, 95% CI = 0.062, 0.354 m/s). ConclusionsDysregulation of the HPA axis measured using salivary cortisol (shallower slope, higher bedtime level) predicted the rate of progression of aortic stiffness among women.

Tumour necrosis factor inhibitors reduce aortic stiffness progression in patients with long-standing rheumatoid arthritis

BackgroundAortic stiffness index (AoSI) has to be considered a proxy outcome measure in patients with rheumatoid arthritis (RA). The aim of this study was to comparatively describe AoSI progression in two groups of RA patients on long-term treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) with or without tumour necrosis factor inhibitors (TNFi).MethodsAoSI was evaluated by Doppler echocardiography at the level of the aortic root, using a two-dimensional guided M-mode evaluation. Eligible participants were assessed at baseline and after 12 months. Changes in serum lipids, glucose and arterial blood pressure were assessed. All patients who did not change DMARD treatment during follow-up were consecutively selected for this study.ResultsWe included 107 (64 TNFi and 43 csDMARDs) RA patients. Most patients (74%) were in remission or low disease activity and had some CVD risk factors (45.8% hypertension, 59.8% dyslipidaemia, 45.3% smoking). The two groups did not differ significantly for baseline AoSI (5.95±3.73% vs 6.08±4.20%, p=0.867). Follow-up AoSI was significantly increased from baseline in the csDMARDs group (+1.00%; p<0.0001) but not in the TNFi group (+0.15%, p=0.477). Patients on TNFi had significantly lower follow-up AoSI from baseline than the csDMARDs group (−1.02%, p<0.001; ANCOVA corrected for baseline AoSI, age and systolic blood pressure). Furthermore, follow-up AoSI was significantly lower in TNFi than in csDMARDs users with an increasing number of CVD risk factors.ConclusionLong-term treatment with TNFi was associated with reduced aortic stiffness progression in patients with established RA and several CVD risk factors.

Evaluation of the Effects of Aging on the Aorta Stiffness in Relation with Mineral and Trace Element Levels: an Optimized Method via Custom-Built Stretcher Device.

Aortic stiffness represents the major cause of aging and tightly associated with hypertension, atherosclerosis, cardiovascular diseases, and increased mortality. Mechanical characteristics of the aorta play a vital role in the blood flow, circulation, systolic pressure, and aortic stiffness; however, the correlation of trace element and mineral levels with aortic stiffness has not been studied before. Balance in the trace elements and minerals is vital for the biological functions; however, natural aging may alter this balance. Thus, after measuring aortic stiffness of aged and young rat aortas by a custom-built stretcher device, trace element and mineral levels were evaluated via ICP-MS. Also, biomarkers of aging including blood pressure, arterial pressure glucose, insulin levels, and histochemical parameters were investigated as well. Aortic stiffness, blood glucose, plasma insulin, systolic, diastolic, and mean arterial pressure significantly increased by aging in the aorta of aged rats compared with the young ones. Also, Fe, Al, Co, Ni, Zn, Sr, Na, Mg, and K levels increased in the aged aorta samples compared with the young aorta samples of rats. Increased levels of the indicated elements may be correlated with the development and progression of aortic stiffness and vascular complications. Thus, possible mechanisms correlating aortic stiffness with the imbalance in the trace element and mineral levels should be further investigated.

Psychological Wellbeing and Aortic Stiffness: Longitudinal Study.

This study investigated 2 distinct aspects of positive wellbeing: affective wellbeing and eudaimonia with progression of aortic stiffness, an index of subclinical cardiovascular disease. A total of 4754 participants (mean age 65.3 years, 3466 men, and 1288 women) from the Whitehall II cohort study provided data on affective and eudaimonic wellbeing using subscales from the control, autonomy, self-realization and pleasure-19 questionnaire. Aortic stiffness was measured by aortic pulse wave velocity (PWV) at baseline (2008-2009) and 5 years later (2012-2013). Linear mixed models were used to measure the effect of affective and eudaimonic wellbeing on baseline PWV and 5-year PWV longitudinal change. A 1-SD higher eudaimonic wellbeing was associated with lower baseline PWV in men (β=-0.100 m/s [95% CI=-0.169 to -0.032]), independent of social, behavioral, and biological factors. This association persisted over 5 years. No such association was found in women (β=-0.029 m/s [95% CI=-0.126 to 0.069]). We did not find any association of positive wellbeing with change in PWV over time in either men or women. In older men, higher levels of eudaimonic wellbeing were associated with lower long-term levels of arterial stiffness. These findings support the notion that the pattern of association between positive wellbeing and cardiovascular health outcomes involves eudaimonic rather than affective wellbeing and is sex-specific.

Pharmacologic Therapies for Aortic Stiffness in End-Stage Renal Disease: A Systematic Review and Meta-Analysis.

Background:Increased carotid-femoral pulse wave velocity (cf-PWV), a surrogate of increased aortic stiffness, is a risk factor for cardiovascular events and all-cause mortality in end-stage renal disease (ESRD). To minimize the deleterious effects of an increased aortic stiffness in ESRD patients, several interventions have been developed and cf-PWV has been used to monitor responses.Objective:The aim of this study was to determine the effects of pharmacologic interventions that target aortic stiffness on cf-PWV and systolic blood pressure (SBP) in adults with ESRD.Study design:This study implements a systematic review and meta-analysis.Data sources:MEDLINE, EMBASE, Cochrane Central, Health Technology Assessment, and EBM databases were searched.Study eligibility, participants, and interventions:Randomized and non-randomized studies involving adults (>18 years) with ESRD of any duration, receiving or not renal replacement therapy (hemodialysis, peritoneal dialysis) and exposed to a pharmacologic intervention whose effects were assessed by cf-PWV.Methods:Study screening, selection, data extraction, and quality assessments were performed by 2 independent reviewers. Narrative synthesis and quantitative data analysis summarized the review.Results:We included 1027 ESRD participants from 13 randomized and 5 non-randomized studies. Most pharmacologic interventions targeted bone mineral metabolism disorder or hypertension. Treatment with vitamin D analogues or cinacalcet did not decrease cf-PWV or SBP over placebo or matched controls (P > .05). Calcium-channel blockers (CCB) decreased cf-PWV and SBP compared with placebo or standard care (P < .05). Renin-angiotensin system inhibitors did not show any advantage over placebo in decreasing cf-PWV (P > .05).Limitations:Quality of evidence ranged from very low to moderate. Overall evidence was limited by the low number of studies, small sample sizes, and methodological inconsistencies.Conclusions:Pharmacologic interventions targeting aortic stiffness in ESRD have mixed effects on reducing cf-PWV, with some strategies suggesting potential benefit. The quality of evidence, however, is insufficient to draw definitive conclusions on their use to slow progression of aortic stiffness in ESRD. Further well-designed studies are needed to confirm these associations and their impact on cardiovascular outcomes in ESRD.Registered in PROSPERO (CRD42016033463)

Two years of maintenance hemodialysis has a pronounced effect on arterial stiffness progression.

The change of aortic stiffness, but not the particular baseline value, plays a crucial role in estimating the patient risk with end-stage renal disease. Therefore, we aimed to analyze the evolution of central and peripheral arterial stiffness in hemodialysis population without previous cardiovascular events during a 2-year follow-up. 60 hemodialysis patients (mean age 57.61 ± 13.01years) were prospectively interviewed, and they underwent blood tests, chest X-ray for aortic calcification evaluation and pulse wave velocity (PWV) measurements at the baseline, after 6months and after 2years of observation period. We found significant progression of aortic PWV (12.73 vs. 14.24m/s, p = 0.032) and regression of brachial PWV (11.53 vs. 8.85m/s, p < 0.001). CRP increase influenced evolution of aortic PWV (β = 0.331, p = 0.031, R2 = 0.599). Higher β2-microglobulin values was related to the progression of aortic PWV (β = 0.219, p = 0.022, R2 = 0.568). Mean arterial blood pressure had influence only on the short-term arterial stiffness evolution. Patients on maintenance hemodialysis experience pronounced changes of arterial stiffness during the 2-year follow-up period. The progression of aortic stiffness is related to inflammatory response and particularly is influenced by β2-microglobulin concentration and aortic calcification.

Autoantibodies against AT1 and α1-adrenergic receptors predict arterial stiffness progression in normotensive subjects over a 5-year period.

Arterial stiffness is an independent indicator of cardiovascular risk. Autoantibodies (AAs) against angiotensin AT1 receptor (AT1-AAs) and α1-adrenergic receptor (α1-AAs) are important in the pathogenesis of hypertension. We identified the types of AT1-AAs and α1-AAs in normotensive subjects, with the aim of determining whether these antibodies predict aortic stiffness progression. Carotid-femoral pulse wave velocity (cf-PWV) was used to measure aortic stiffness. Overall, 816 subjects (71% of those invited) underwent a medical examination and evaluation of aortic stiffness. The types of AT1-AAs and α1-AAs were measured at baseline. Meanwhile, plasma renin, angiotensin II (Ang II), and norepinephrine (NE) concentrations were measured at baseline and follow-up. Baseline mean cf-PWV was 9.90 ± 0.84 m/s and follow-up was 10.51 ± 1.12 m/s. The annualized ΔPWV was 0.12 ± 0.08 m/s/year. At the end of follow-up, 129 normotensive subjects developed hypertension and 144 subjects had PWV progression. After adjustment for covariates, AA type was independently associated with ΔPWV, annualized ΔPWV, and abnormal PWV. In our study, the risk of developing hypertension (RR =2.028, 95% CI: 1.227-3.351, P=0.006) and PWV progression (RR =2.910, 95% CI: 1.612-5.253, P<0.001) in AA-positive subjects was significantly higher than that in AA-negative subjects. Receiver operating characteristic (ROC) curve showed AA had an identify power to discriminate subjects with or without PWV and hypertension progression. We have shown for the first time that the types of A1-AAs and α1-AAs are independent predictors for aortic stiffness progression in normotensive subjects. Our data collectively support the utility of these AAs as potential markers of aortic stiffness.

Greater Progression of Age-Related Aortic Stiffening in Adults with Poor Trunk Flexibility: A 5-Year Longitudinal Study.

Purpose: Having a low level of physical fitness, especially cardiorespiratory fitness, appears to accelerate age-related aortic stiffening. Whereas, some studies have reported that trunk flexibility is a component of physical fitness, it is also negatively associated with arterial stiffening independent of cardiorespiratory fitness in cross-sectional studies. However, no long-term longitudinal study has determined whether poor trunk flexibility accelerates the progression of age-related aortic stiffening. We examined trunk flexibility and aortic stiffness progression in a 5-year longitudinal study.Methods and Results: A total of 305 apparently healthy men and women participated in this study (49.6 ± 9.5 years of age). Trunk flexibility was measured using a sit-and-reach test. Aortic stiffness was assessed using carotid-femoral pulse wave velocity (cfPWV) at baseline and after 5 years. Analysis of covariance (ANCOVA) was used to assess the association of the annual rate of cfPWV across flexibility levels (low, middle, high). There were no significant differences in baseline cfPWV among the three groups (835 ± 164, 853 ± 140, 855 ± 2.68 cm/s; P = 0.577). Annual ΔcfPWV was significantly higher in the low-flexibility group than in the high-flexibility group (P = 0.009). ANCOVA revealed an inverse relationship between flexibility level and annual ΔcfPWV (14.41 ± 2.73, 9.79 ± 2.59, 2.62 ± 2.68 cm/s/year; P for trend = 0.011). Multiple regression analysis revealed that baseline sit and reach (β = −0.12, −0.70 to −0.01) was independently correlated with ΔcfPWV following adjustment for baseline peak oxygen uptake, age, sex, body fat, heart rate, and cfPWV. The 5-year change in cfPWV was not significantly correlated with 5-year change in sit-and-reach performance (P = 0.859).Conclusion: Poor trunk flexibility is associated with greater progression of age-related aortic stiffening in healthy adults. However, we failed to confirm a significant association between 5-year change in aortic stiffness and 5-year change in trunk flexibility. The association between increased age-related increase in aortic stiffness and deterioration in flexibility due to age may require observation for more than 5 years.

Baseline predictors of aortic stiffness progression among multi-ethnic Asians with type 2 diabetes

Background and aimsThis 3-year prospective study aimed to identify baseline parameters that predicted the progression of carotid-femoral pulse wave velocity (cf-PWV), which was used to evaluate aortic stiffness, among Singapore's multi-ethnic Asians with type 2 diabetes (T2DM). MethodsThe cf-PWV was measured by the gold-standard tonometry method in 994 T2DM subjects at baseline and follow-up. The annual rate of cf-PWV change was calculated, and individuals above the 90th percentile with rate≥1.42 m/s per year were regarded as rapid progressors (n = 104). In a subgroup analysis of subjects with normal cf-PWV at 1st visit (n = 611), incident aortic stiffness was defined as follow-up cf-PWV≥10 m/s (n = 188). ResultsThe total cohort (mean age:57 ± 10 years; 53.4% Chinese, 20.4% Malay, 22.9% Indian, 3.2% ‘Others’) displayed a median annual cf-PWV progression rate of 0.2 m/s. Adjusted multivariate regression analyses showed that baseline age, cf-PWV and body mass index (BMI) constantly predicted follow-up cf-PWV, annual cf-PWV progression rate, rapid cf-PWV progression, and incident aortic stiffness. Paradoxically, lower baseline cf-PWV was associated with elevated annual cf-PWV progression rate and rapid progressors. This inverse relationship remained significant across ethnicities after ethnic stratification. Higher BMI independently predicted cf-PWV progression in Chinese and Indians, but not in Malay and ‘Others’ ethnic groups. Increased age was a significant predictor in Chinese and ‘Others’ ethnicities. ConclusionsWe demonstrated that baseline BMI is a modifiable independent risk factor of cf-PWV progression and incident aortic stiffness. Therefore, better obesity management may impede aortic stiffness in Singapore's T2DM patients, especially in the Chinese and Indians.

Nondiabetic Glucometabolic Status and Progression of Aortic Stiffness: The Whitehall II Study.

OBJECTIVEAortic stiffness is an important predictor of future morbidity and mortality. Diabetes is associated with increased aortic stiffness, but the importance of nondiabetic glucometabolic status for accelerated aortic stiffening is unclear. We tested the hypothesis that adverse glucometabolic status is associated with accelerated aortic stiffening in individuals without diabetes, independently of known risk factors for arterial stiffening.RESEARCH DESIGN AND METHODSGlucometabolic status and other cardiovascular risk factors were assessed at baseline in 2008–09, and carotid femoral pulse wave velocity (cfPWV) at baseline and follow-up in 2012–13, in 4,386 participants without diabetes of the Whitehall II Study.RESULTSThe mean age of the cohort at cfPWV baseline was 60 years, and 74% were male. cfPWV increased from (mean ± SE) 8.30 ± 0.03 to 8.98 ± 0.04 m/s during 4 years of follow-up. At baseline, cfPWV was associated with fasting and 2-h postload glucose, HbA1c, and HOMA-insulin resistance (HOMA-IR). HbA1c and HOMA-IR were associated with progression of cfPWV after adjusting for physiological confounders and cardiovascular risk factors. A 1 SD higher HbA1c and HOMA-IR were associated with greater increases in cfPWV (0.11 m/s per 5 years [95% CI 0.04, 0.18], P = 0.003 and 0.09 m/s per 5 years [0.01, 0.17], P = 0.03, respectively). Additional adjustment for BMI weakened the association with HOMA-IR but not with HbA1c.CONCLUSIONSHbA1c is independently associated with accelerated progression of aortic stiffness in individuals without diabetes. These findings suggest that long-term glucometabolic status, even in individuals without diabetes, could be an important target for preventative strategies against vascular aging.

Abstract 13728: Poor Trunk Flexibility is Associated With Greater Progression of Age-related Arterial Stiffening: A 5-year Longitudinal Study

Introduction: Low level of physical fitness, especially cardiorespiratory fitness, appear to accelerate age-related aortic stiffening. Whereas, some studies have reported that flexibility, is one of the components of physical fitness, is also associated with arterial stiffening independent of cardiorespiratory fitness in cross sectional studies. However, no longitudinal study has determined whether poor trunk flexibility might accelerate the progression of age-related aortic stiffening. Hypothesis: Poor trunk flexibility is associated with greater progression of age-related aortic stiffening in apparently healthy adults. Methods: We examined trunk flexibility and aortic stiffness progression in a 5-year follow-up study of 361 healthy men and women aged 27-73 years. Trunk flexibility was measured by a sit-and-reach test. Aortic stiffness was assessed using carotid-femoral pulse wave velocity (cfPWV) at baseline and after 5 years. To assess the effects of flexibility level on the progression of aortic stiffening, the participants were categorized into tertiles (Low, Middle, High) based on their sit-and-reach test values at baseline. ANCOVA was used to analyze the association of the annual rate of cfPWV (cm/ sec/ year) [annual ΔcfPWV = (follow-up cfPWV- baseline cfPWV) / follow-up years] across flexibility levels. Baseline age, BMI, cfPWV, brachial systolic blood pressure, cardiorespiratory fitness and sex were entered as covariates for adjustment. Results: The annual ΔcfPWV was significantly greater in the low (poor) flexibility group (10.95±2.49 cm/sec/year) than in the high flexibility group (2.19±2.41 cm/sec/year) (P=0.041). An inverse relationship was observed between flexibility level and the annual ΔcfPWV (P for trend = 0.042). The multiple regression analysis revealed that baseline sit and reach (β = -0.125), age (β = 0.197), cfPWV (β = - 0.432), cardiorespiratory fitness (β = -0.144), and sex (β = - 0.174) were independent correlates of ΔcfPWV. These data indicate that flexibility is associated with aortic stiffness, independent of other factors already known to be related to arterial stiffness. Conclusions: Poor flexibility is associated with greater progression of age-related aortic stiffening.

Socioeconomic status, education, and aortic stiffness progression over 5 years: the Whitehall II prospective cohort study.

Objective:The inverse association between socioeconomic status (SES) and cardiovascular disease (CVD) risk is well documented. Aortic stiffness assessed by aortic pulse wave velocity (PWV) is a strong predictor of CVD events. However, no previous study has examined the effect of SES on arterial stiffening over time. The present study examines this association, using several measures of SES, and attained education level in a large ageing cohort of British men and women.Methods:Participants were drawn from the Whitehall II study. The sample was composed of 3836 men and 1406 women who attended the 2008–2009 clinical examination (mean age = 65.5 years). Aortic PWV was measured in 2008–2009 and in 2012–2013 by applanation tonometry. A total of 3484 participants provided PWV measurements on both occasions. The mean difference in 5-year PWV change was examined according to household income, education, employment grade, and father's social class, using linear mixed models.Results:PWV increase [mean: confidence interval (m/s)] over 5 years was higher among participants with lower employment grade (0.38: 0.11–0.65), household income (0.58, 95%: 0.32–0.85), and education (0.30: 0.01, 0.58), after adjusting for sociodemographic variables, BMI, alcohol consumption, smoking, and other cardiovascular risk factors, namely SBP, mean arterial pressure, heart rate, cholesterol, diabetes, and antihypertensive use.Conclusion:The present study supports the presence of robust socioeconomic disparities in aortic stiffness progression. Our findings suggest that arterial aging could be an important pathophysiological pathway explaining the impact of lower SES on CVD risk.

PP.20.28

Objective: We have previously shown that there is a blood pressure independent reduction in aortic stiffness as early as 3 months after successful a kidney transplantation (KTx). The purpose of the present study is to examine the effects of KTx on changes in aortic stiffness after 2 years of follow-up. Design and method: In this prospective, longitudinal observational study, we studied hemodynamic and biological parameters prior to KTx and 3, 6 and 24 months after a KTx in 59 dialysis patients. Aortic stiffness was measured by carotid-femoral pulse wave velocity (cf-PWV). A successful kidney transplant was defined by an estimated eGFR of 45 or more mL/min/1.732 at the time of the measurement of aortic stiffness. A GEE model was used to take into account the repeated measures of aortic stiffness and mean blood pressure. Values are reported as mean ± SEM unless otherwise specified. Results: The mean age was 48 ± 14 years, with 70% male, 20% with cardiovascular disease and 25% diabetes. After adjusting for mean blood pressure, cf-PWV decreased significantly from 11.2 ± 0.33 to 10.3 ± 0.30 by 3 months (P = 0.042), but it increased to 10.8 ± 0.31 and 11.2 ± 0.33 (m/s) by 6 and 24 months (P = NS versus preKTx). The rate of progression of aortic stiffness beyond 3 months was 0.248 m/s/year.Conclusions: After an initial improvement of aortic stiffness, there is a progression of aortic stiffness that is numerically lower than what has been previously been reported in dialysis population.

Correlates of aortic stiffness progression in patients with resistant hypertension: importance of clinic and ambulatory blood pressure changes.

Correlates of serial aortic stiffness changes were scarcely evaluated. We aimed to evaluate them in patients with resistant hypertension, with particular attention to the importance of changes in clinic and ambulatory blood pressures (BP). In a prospective study, two carotid-femoral pulse wave velocity (cf-PWV) measurements (three measures in each occasion) were performed with the Complior equipment in 442 resistant hypertensive patients over a mean follow-up of 4.6 years. Multivariable regressions assessed the independent correlates of changes in cf-PWV. All analyses were further adjusted for baseline cf-PWV and BP values, and for the time interval between measurements. Carotid-femoral PWV had a median increase of 0.11 m/s per year (1.1% per year). Overall, 224 patients (51%) had an increase or persisted with high cf-PWV, whereas 218 (49%) reduced or persisted with low values. On multivariable regressions, both changes in clinic SBP (partial correlation 0.34, P < 0.001) and in 24-h SBP (partial correlation 0.40, P < 0.001) were correlates of changes in cf-PWV. This means that the white-coat effect, defined as the difference between clinic and daytime BPs, affected cf-PWV changes (partial correlation 0.19, P < 0.001). The other independent correlates of aortic stiffness progression were older age, presence of diabetes, higher waist circumference and worse renal function. The exaggerated white-coat effect, by acutely increasing clinic BPs during cf-PWV examination, may partially obscure the beneficial effects of reducing ambulatory BP levels on aortic stiffness attenuation. Arterial stiffness measurements under ambulatory conditions may be needed to correctly assess aortic stiffness changes in resistant hypertensive patients.

Correlates of aortic stiffness progression in patients with type 2 diabetes: importance of glycemic control: the Rio de Janeiro type 2 diabetes cohort study.

The correlates of serial changes in aortic stiffness in patients with diabetes have never been investigated. We aimed to examine the importance of glycemic control on progression/regression of carotid-femoral pulse wave velocity (cf-PWV) in type 2 diabetes. In a prospective study, two cf-PWV measurements were performed with the Complior equipment in 417 patients with type 2 diabetes over a mean follow-up of 4.2 years. Clinical laboratory data were obtained at baseline and throughout follow-up. Multivariable linear/logistic regressions assessed the independent correlates of changes in cf-PWV. Median cf-PWV increase was 0.11 m/s per year (1.1% per year). Overall, 212 patients (51%) increased/persisted with high cf-PWV, while 205 (49%) reduced/persisted with low cf-PWV. Multivariate linear regression demonstrated direct associations between cf-PWV changes and mean HbA1c during follow-up (partial correlation 0.14, P = 0.005). On logistic regression, a mean HbA1c ≥7.5% (58 mmol/mol) was associated with twofold higher odds of having increased/persistently high cf-PWV during follow-up. Furthermore, the rate of HbA1c reduction relative to baseline levels was inversely associated with cf-PWV changes (partial correlation -0.11, P = 0.011) and associated with reduced risk of having increased/persistently high aortic stiffness (odds ratio 0.82 [95% CI 0.69-0.96]; P = 0.017). Other independent correlates of progression in aortic stiffness were increases in systolic blood pressure and heart rate between the two cf-PWV measurements, older age, female sex, and presence of dyslipidemia and retinopathy. Better glycemic control, together with reductions in blood pressure and heart rate, was the most important correlate to attenuate/prevent progression of aortic stiffness in patients with type 2 diabetes.