Higher Aortic Pulse Wave Velocity Research Articles

Sex Differences in Central Hemodynamics of Patients with Untreated Obstructive Sleep Apnea

Patients with obstructive sleep apnea (OSA) have increased risk for cardiovascular diseases. Data from the Atherosclerosis Risk in the Communities and Sleep Heart Health Study suggest that OSA is more deleterious to females versus males, although mechanistic data are lacking. Estimates of central (aortic) blood pressure (BP) are superior in predicting future cardiovascular events than traditional brachial BP measurements. While patients with OSA have altered central hemodynamics (e.g., higher aortic pulse wave velocity; PWV), potential sex differences are unexplored. We tested the hypothesis that females with OSA (n=7, 50±3yrs, 35.1±1.9kg/m2, 22.2±7.6 events/hr) have worse central hemodynamics than males with OSA (n=9, 47±3yrs, 35.0±1.4kg/m2, 31.7±6.2 events/hr). Data collection consisted of an overnight sleep study (polysomnography) to identify the presence, and characterize the severity, of OSA via the apnea-hypopnea index (AHI). Then, duplicate measures of central (aortic) and peripheral (brachial) BP, as well as central artery stiffness (PWV) and wave reflection (AIx), were made in the morning after ≥15min of quiet, supine rest. Additional hemodynamic measurements were made if data differed by ≥2% (AIx) or ≥0.5m/s (PWV). Data that met these criteria were averaged and used for analysis. Comparisons were made using two-tailed, independent samples t-tests or nonparametric Mann-Whitney Rank Sum tests, as indicated. No differences were observed in age (p=0.44), body mass index (p=0.96), nor AHI (p=1.00) between sexes. Similarly, no sex differences were observed in brachial systolic (female vs. male: 129±7 vs. 134±8mmHg, p=0.83), diastolic (77±5 vs. 85±4mmHg, p=0.26), or mean BP (96±6 vs. 101±5mmHg, p=0.45). Similarly, central systolic (122±6 vs. 125±7mmHg, p=0.96), diastolic (78±5 vs. 86±4mmHg, p=0.25), and augmentation (21±2 vs. 15±2mmHg, p=0.07) BP did not differ between sexes. Resting heart rate was also comparable between groups (67±3 vs. 65±2bpm, p=0.64). However, AIx (AIx; 42±3 vs. 35±4%) and AIx normalized to a heart rate of 75bpm (42±3 vs. 30±3%) were higher in females with OSA relative to males with OSA (p<0.05 for both). Interestingly, the forward (30±3 vs. 28±2mmHg, p=0.63) and reflected (20±2 vs. 18±2mmHg, p=0.44) pulse heights, as well as PWV (7.3±0.6 vs. 7.4±0.6m/s, p=0.85), were similar between groups. Our data indicate that despite a trend towards higher BP in males with OSA (~5mmHg) that may be clinically, though not statistically different, females with OSA have a higher AIx. As AIx is positively associated with left ventricular hypertrophy, these data also suggest that altered central (aortic) hemodynamics may contribute to the sex differences in cardiovascular risk with OSA. This work was supported by the National Institutes of Health T32-HL007111 and U54AG044170 (JMB), HL065176 (PS and VKS), and HL134885 (VKS). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Diabetes mellitus modifies the association between chronic kidney disease-mineral and bone disorder biomarkers and aortic stiffness in peritoneal dialysis patients.

This study aimed to investigate the relationship of four chronic kidney disease-mineral and bone disorder (CKD-MBD) biomarkers, including intact parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), soluble klotho, and fetuin-A, with aortic stiffness in peritoneal dialysis (PD) patients, comparing those with and without diabetes mellitus (DM). A total of 213 patients (mean age 58 ± 14years; 81 (38.0%) patients with DM) were enrolled. Their aortic pulse wave velocity (PWV) was measured using pressure applanation tonometry, while serum intact PTH, FGF23, α-klotho, and fetuin-A levels were measured using enzyme-linked immunosorbent assay. Overall, patients with DM had higher aortic PWV than those without (9.9 ± 1.8 vs. 8.6 ± 1.4m/s, p < 0.001). Among the four CKD-MBD biomarkers, FGF23 levels were significantly lower in DM group (462 [127-1790] vs. 1237 [251-3120] pg/mL, p = 0.028) and log-FGF23 independently predicted aortic PWV in DM group (β: 0.61, 95% confidence interval: 0.06-1.16, p = 0.029 in DM group; β: 0.10, 95% confidence interval: - 0.24-0.45, p = 0.546 in nonDM group; interaction p = 0.016). In conclusion, the association between FGF23 and aortic PWV was significantly modified by DM status in PD patients.

Type III aortic arch angulation increases aortic stiffness: Analysis from an ex vivo porcine model

ObjectiveThe relationship among increased aortic arch angulation, aortic flow dynamics, and vessel wall stiffness remains unclear. This experimental ex vivo study investigated how increased aortic arch angulation affects aortic stiffness and stent-graft induced aortic stiffening, assessed by pulse wave velocity (PWV). MethodsPorcine thoracic aortas were connected to a circulatory mock loop in a Type I and Type III aortic arch configuration. Baseline characteristics and blood pressures were measured. Proximal and distal flow curves were acquired to calculate PWV in both arch configurations. After that, a thoracic stent-graft (VAMF2626C100TU) was deployed in aortas with adequate proximal landing zone diameters to reach 10% t0 20% oversizing. Acquisitions were repeated for both arch configurations after stent-graft deployment. ResultsTwenty-four aortas were harvested, surgically prepared, and mounted. Cardiac output was kept constant for both arch configurations (Type I: 4.74 ± 0.40 and Type III: 4.72 ± 0.38 L/minute; P = .703). Compared with a Type I arch, aortic PWV increased significantly in the Type III arch (3.53 ± 0.40 vs 3.83 ± 0.40 m/second; P < .001), as well as blood pressures. A stent-graft was deployed in 15 aortas. After deployment, Type I arch PWV increased (3.55 ± 0.39 vs 3.81 ± 0.44 m/second; P < .001) and Type III arch PWV increased although not significantly (3.86 ± 0.42 vs 4.03 ± 0.46 m/second; P = .094). Type III arch PWV resulted the highest and significantly higher compared with the Type I arch after stent-graft deployment (3.81 ± 0.44 vs 4.03 ± 0.46 m/second; P = .023). ConclusionsIncreased aortic arch angulation—as in a Type III arch—is associated with higher aortic PWV and blood pressures and this may negatively influence cardiovascular health.

Preclinical Aortic Atherosclerosis in Adolescents With Chronic Disease.

Background Adolescents with chronic disease are often exposed to inflammatory, metabolic, and hemodynamic risk factors for early atherosclerosis. Since postmortem studies have shown that atherogenesis starts in the aorta, the CDACD (Cardiovascular Disease in Adolescents with Chronic Disease) study investigated preclinical aortic atherosclerosis in these adolescents. Methods and Results The cross-sectional CDACD study enrolled 114 adolescents 12 to 18years old with chronic disorders including juvenile idiopathic arthritis, cystic fibrosis, obesity, corrected coarctation of the aorta, and healthy controls with a corrected atrial septal defect. Cardiovascular magnetic resonance was used to assess aortic pulse wave velocity and aortic wall thickness, as established aortic measures of preclinical atherosclerosis. Cardiovascular magnetic resonance showed a higher aortic pulse wave velocity, which reflects aortic stiffness, and higher aortic wall thickness in all adolescent chronic disease groups, compared with controls (P<0.05). Age (β=0.253), heart rate (β=0.236), systolic blood pressure (β=-0.264), and diastolic blood pressure (β=0.365) were identified as significant predictors for aortic pulse wave velocity, using multivariable linear regression analysis. Aortic wall thickness was predicted by body mass index (β=0.248) and fasting glucose (β=0.242), next to aortic lumen area (β=0.340). Carotid intima-media thickness was assessed using ultrasonography, and was only higher in adolescents with coarctation of the aorta, compared with controls (P<0.001). Conclusions Adolescents with chronic disease showed enhanced aortic stiffness and wall thickness compared with controls. The enhanced aortic pulse wave velocity and aortic wall thickness in adolescents with chronic disease could indicate accelerated atherogenesis. Our findings underscore the importance of the aorta for assessment of early atherosclerosis, and the need for tailored cardiovascular follow-up of children with chronic disease.

The stiff male arterial system seems to establish itself well before puberty

Abstract Background Increased vascular stiffness in adults is associated with symptomatic cardiovascular disease independently of other risk factors. From puberty and onwards, men have higher aortic pulse-wave velocity than women explaining part of the male overrepresentation of early cardiovascular disease. It is not known if the stiff male arterial system is related to adult life-style or develops under the influence of male hormones, or if it is already present before puberty. According to the hyperbolic Bramwell-Hill relation, early changes must be expected to become detectable in aortic distensibility before influencing aortic pulse-wave velocity. Purpose The objective of this study was to quantitate sex-related differences in aortic distensibility and pulse-wave velocity in pre-pubertal children. Methods 150 children aged 8–9 years (75 girls and 75 boys) were recruited to a cardiovascular magnetic resonance imaging (CMR) study of the importance of in vitro fertilization (IVF) for aortic distensibility. Data did not show differences related to the mode of conception (natural vs. IVF), and pooled data are reported here. Conductance artery stiffness was determined from ascending, descending and abdominal aorta distensibility and from arch and abdominal aorta pulse-wave velocity (PWV). Data were analyzed blinded to child sex and mode of conception and related to left heart function as determined from flow and volumetric CMR data. The effects of sex on ascending aorta distensibility and total aortic PWV were examined in four linear regression models by stepwise adjustment for potential confounders. Results Systolic and diastolic blood pressures, cardiac output and total peripheral resistance did not differ between the sexes. Pulse pressure, however, was a mean of 2 mmHg lower and heart rate 7 bpm higher in girls (Table 1), and corresponding to the lower heart rate, left ventricle (LV) end-diastolic volume index and left ventricle stroke volume were 7 mL and 5 mL, respectively, higher in boys. LV peak-filling rate indexed to LV end-diastolic volume was 0.5 s-1 lower in boys, but in general LV filling and left atrium emptying parameters were equal. Distensibility of the ascending and descending aorta were both significantly higher in girls as compared to boys, whereas boys and girls had equal abdominal aortic distensibility and equal aortic pulse-wave velocities. Distensibility of the ascending aorta remained statistically significant after adjustment for potential confounders (Table 2). Conclusion Without yet significantly affecting pulse wave velocity or left ventricle function, pre-pubertal boys had significantly lower distensibility of the ascending aorta and the aortic arch than pre-pubertal girls. This is the part of the aorta primarily responsible for the aortic Windkessel function, and it seems that the stiffer arterial system seen in adult men as compared to adult women may already be present in childhood well before puberty. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Foundation Table 1Table 2

Long-Term Effects of Renal Artery Denervation.

Background and Objectives: Renal artery denervation (RDN) procedure is a broadly discussed method in the treatment of resistant hypertension. Many studies report short-term (3–12 months) results for blood pressure and arterial stiffness. The primary endpoints were changes in 24 h mean systolic blood pressure (BP) and office systolic BP 48 months after RDN. The secondary endpoints were changes in aortic pulse wave velocity and impact of polypharmacy on these variables. Materials and Methods: Renal artery denervation was performed in 73 patients treated for resistant hypertension; 49 patients remained in final analysis. Patient examination was carried out before the procedure, and subsequently at 3, 6, 12, 24, and 48 months later. Patients’ antihypertensive and overall medication regimens were carefully analysed. Results: Mean 24 h arterial blood pressure lowered and was sustained at lower levels for up to 48 months; median (interequartile range—IQR) from 158(23.5)/100(14.2) to 140(26.5)/86(16.2) mmHg. Mean reduction in 24 h ambulatory systolic BP was −11 ± 25 mmHg (95% CI, −20 to −2; p < 0.001), while office systolic BP reduced by −7 ± 23 mmHg (95%CI, −24 to −1; p < 0.02). A significant reduction in median aortic pulse wave velocity 12 months after the procedure (drop from baseline 11.2 [3.15] m/s (95%CI 6.1 to 16.2) to 9.8 [2.1] m/s (95%CI 6.1 to 13.7; p = 0.002)). After 48 months, there was no worsening compared to the baseline level of 10.3 [4.0] m/s (95% CI 6.9 to 17.8) (p > 0.05). The total mean number of antihypertensive drugs remained unchanged: 5.97(±1.1) vs. 5.24 (±1.45). A higher number of pills after 48 months was associated with higher aortic pulse wave velocity (1–5 pill group: 8.1 ± 1.6 m/s; 6–10 pill group: 10.9 ± 1.8 m/s; >11 pill group: 15.1 ± 2.6 m/s) (p = 0.003). Conclusions: Antihypertensive effect after renal denervation lasts up to 48 months with no worsening of arterial stiffness compared to baseline. In our study, polypharmacy was associated with increased arterial stiffness 48 months after the procedure.

Apigenin restores endothelial function by ameliorating oxidative stress, reverses aortic stiffening, and mitigates vascular inflammation with aging.

We assessed the efficacy of oral supplementation with the flavanoid apigenin on arterial function during aging and identified critical mechanisms of action. Young (6 mo) and old (27 mo) C57BL/6N mice (model of arterial aging) consumed drinking water containing vehicle (0.2% carboxymethylcellulose; 10 young and 7 old) or apigenin (0.5 mg/mL in vehicle; 10 young and 9 old) for 6 wk. In vehicle-treated animals, isolated carotid artery endothelium-dependent dilation (EDD), bioassay of endothelial function, was impaired in old versus young (70% ± 9% vs. 92% ± 1%, P < 0.0001) due to reduced nitric oxide (NO) bioavailability. Old mice had greater arterial reactive oxygen species (ROS) production and oxidative stress (higher nitrotyrosine) associated with greater nicotinamide adenine dinucleotide phosphate oxidase (oxidant enzyme) and lower superoxide dismutase 1 and 2 (antioxidant enzymes); ex vivo administration of Tempol (antioxidant) restored EDD to young levels, indicating ROS-mediated suppression of EDD. Old animals also had greater aortic stiffness as indicated by higher aortic pulse wave velocity (PWV, 434 ± 9 vs. 346 ± 5 cm/s, P < 0.0001) due to greater intrinsic aortic wall stiffness associated with lower elastin levels and higher collagen, advanced glycation end products (AGEs), and proinflammatory cytokine abundance. In old mice, apigenin restored EDD (96% ± 2%) by increasing NO bioavailability, normalized arterial ROS, oxidative stress, and antioxidant expression, and abolished ROS inhibition of EDD. Moreover, apigenin prevented foam cell formation in vitro (initiating step in atherosclerosis) and mitigated age-associated aortic stiffening (PWV 373 ± 5 cm/s) by normalizing aortic intrinsic wall stiffness, collagen, elastin, AGEs, and inflammation. Thus, apigenin is a promising therapeutic for arterial aging.NEW & NOTEWORTHY Our study provides novel evidence that oral apigenin supplementation can reverse two clinically important indicators of arterial dysfunction with age, namely, vascular endothelial dysfunction and large elastic artery stiffening, and prevents foam cell formation in an established cell culture model of early atherosclerosis. Importantly, our results provide extensive insight into the biological mechanisms of apigenin action, including increased nitric oxide bioavailability, normalization of age-related increases in arterial ROS production and oxidative stress, reversal of age-associated aortic intrinsic mechanical wall stiffening and adverse remodeling of the extracellular matrix, and suppression of vascular inflammation. Given that apigenin is commercially available as a dietary supplement in humans, these preclinical findings provide the experimental basis for future translational studies assessing the potential of apigenin to treat arterial dysfunction and reduce cardiovascular disease risk with aging.

Abstract 14090: Multiparity is Associated With Aortic Pathology in Women From the Dallas Heart Study

Introduction: The proximal aorta has been shown to enlarge with aging in humans, but the long-term impact of hormonal and hemodynamic changes associated with pregnancy on aortic size and function are unknown. We examined if number of live births was independently associated with aortic dimensions and stiffness in a healthy multi-ethnic population-based cohort, the Dallas Heart Study (DHS). We hypothesized that multiparity (&gt;/=4 live births) is independently associated with aortic dilation and aortic stiffness after adjustment for CV risk factors. Methods: Women with available thoracic aortic MRI measurements (n=1468, mean 44.5 years old) from DHS were stratified based on self-reported number of live births (0,1,2,3,&gt;/=4). Sequential multivariable logistic regression models were used to assess independent associations of the number of live births with ascending aortic cross-sectional area/height, aortic pulse wave velocity (PWV) and aortic compliance. Models were adjusted for major CV risk factors. Results: Women with &gt;/=4 live births were older, more likely to be Black, and had higher blood pressure, triglycerides and body mass index. Compared with nulliparous women, women with &gt;/=4 had larger ascending aortic areas indexed to height [5.19 vs 4.74 cm2/m; p&lt;0.0001; Table 1]. After adjustment for risk factors, multiparity remained a significant predictor of aortic size. Compared to nulliparous women, women with &gt;/=4 live births also had higher aortic PWV (5.54 vs 4.54 m/s; p&lt;0.0001) and lower aortic compliance (21.9 vs 27.2 mL/mmHg; p 0.0002), but these relationships were no longer significant after multivariable adjustment (Table 1). Analyzing live births as a continuous variable did not change these results. Conclusions: Multiparity was associated with thoracic aortic enlargement, independent of age and relevant risk factors. Parity is an emerging sex-specific risk factor in cardiovascular disease that may have an impact on aortic remodeling in women.

Increased arterial stiffness in males with abdominal aortic aneurysm

BackgroundAbdominal aortic aneurysm (AAA), a localized dilatation of the abdominal aorta, has a prevalence of about 1.5%–3% among 65‐ to 70‐year‐old males in Europe. AAA confers an increased risk of developing major cardiovascular events in addition to the risk of aneurysm rupture. The aim of this study was to evaluate whether the arterial wall distensibility is altered in subjects with AAA.MethodsTwo hundred and eighty‐four male subjects (182 with AAA and 102 controls) were enrolled in the study. Arterial wall distensibility was evaluated using non‐invasive applanation tonometry to measure regional pulse wave velocity between the carotid and femoral arteries and the carotid and radial arteries. In addition, blood pressure was measured, and the pulse pressure waveform was analysed.ResultsHigher aortic augmentation index (25.1% versus 20.6%; p < .001) and higher aortic pulse wave velocity (12.3 m/s versus 10.9 m/s; p < .001) were demonstrated in the AAA cohort. The slightly higher arm pulse wave velocity in the AAA group (9.4 m/s versus 9.1 m/s; p < .05) was abolished after adjusting for mean arterial blood pressure.ConclusionsMales with AAA have decreased aortic wall distensibility and enhanced reflection waves in central aorta during systole. These results imply that increased arterial wall stiffness may be a contributing factor to the overall higher cardiovascular risk seen in patients with AAA.

A3101 The association between early morning hypertension and stroke –related dementia in the elderly

Objectives: We evaluated the prevalence of the pattern of high blood pressure and effects of arterial stiffness, pulse wave velocity (PWV) and wave reflections on central aortic pressure (CAP) in hypertensive patients with dementia. Methods: We analyzed 150 hypertensive patients with dementia, investigated using 24hr ambulatory blood pressure monitoring (ABPM). Among the HT, classified as early morning hypertension (EMHT) (early morning BP: above 135/85 mmHg and night-time BP: below 120/70 mmHg), Night HT (NHT)(Daytime BP: below 135/85 mmHg and night-time BP: above 120/70 mmHg). And using radial artery applanation tonometry, aortic pulse analysis was performed. Results: 85 patients was observed HT with stroke related dementia. EMHT was found in 55.6% of patients. Compared with patients with both EMHT and NHT, EMHT had higher aortic pulse wave velocity (PWV) and augmentation index (AI) and AI75 (AI to HR 75 beat/min), ASP (Central aortic systolic pressure) and pulse pressure were also higher in the EMHT. Conclusion: Our study showed that EMHT could have increased stroke related dementia and especially, early morning systolic BP, might be risk factor for cognitive decline. Hence active anti-hypertension treatment benefits prevention of cognitive dysfunction in stroke related dementia.

Progression of arterial stiffness is associated with changes in bone mineral markers in advanced CKD

BackgroundArterial stiffness is an independent predictor of all-cause and cardiovascular mortality in patients with chronic kidney disease (CKD). There are limited prospective data however on progression of arterial stiffness in CKD, including evaluating associations with bone mineral markers such as fibroblast growth factor 23 (FGF23) and soluble α-klotho (sKl).MethodsIn this prospective, single-center, observational study, arterial stiffness [measured by pulse wave velocity (PWV)] and hormones influencing mineral homeostasis, including serum FGF23 and sKl, were compared between non-dialysis CKD stages 4/5 and healthy controls at baseline and 12 months (12 m). Abdominal aortic calcification (AAC) was quantitated using lateral lumbar radiography at baseline.ResultsForty patients with CKD [mean estimated glomerular filtration rate (eGFR) 19.5 ± 6.7 mL/min/1.73m2] and 42 controls (mean eGFR 88.6 ± 12.9 mL/min/1.73m2) completed follow-up. There were no differences in age, gender and body mass index between groups. A significant increase in FGF23 [240.6 (141.9–1129.8) to 396.8 (160.3–997.7) pg/mL, p = 0.001] was observed in the CKD group but serum phosphate, corrected calcium, parathyroid hormone and sKl did not change significantly over 12 m. At baseline, CKD subjects had higher AAC prevalence [83.8% versus (vs.) 43.6%, p = 0.002] and higher aortic PWV [9.7(7.6–11.7) vs. 8.1 (7.2–9.7) m/s, p = 0.047] compared to controls. At 12 m, aortic PWV increased by 1.3 m/s (95% confidence interval, 0.56 to 2.08, p < 0.001) in the CKD cohort, with 30% of subjects showing progression from normal aortic elasticity to stiffening (PWV > 10 m/s). Serum FGF23 was associated with AAC, abnormal PWV and progression of PWV at 12 m.ConclusionsArterial stiffness and serum FGF23, both of which are associated with increased cardiovascular risk, increased over one year in individuals with CKD. Additionally, a significant association was found between serum FGF23 and arterial calcification and stiffness. Larger clinical studies and further experimental work are warranted to delineate the temporal relationship as well as the pathological mechanisms linking FGF23 and vascular disease.

Influence of Thoracic Aortic Inflammation and Calcifications on Arterial Stiffness and Cardiac Function in Older Subjects.

Vascular aging is accompanied by gradual remodeling affecting both arterial and cardiac structure and mechanical properties. Hypertension is suggested to exert pro-inflammatory actions enhancing arterial stiffness. To determine the influence of thoracic aortic inflammation and calcifications on arterial stiffness and cardiac function in hypertensive and normotensive older subjects. A prospective study. An acute geriatrics ward of the University Hospital of Nancy in France. Thirty individuals ≥ 65 years were examined, including 15 hypertensive subjects and 15 controls well-matched for age and sex. Applanation tonometry was used to measure aortic pulse wave velocity (AoPWV) and carotid/brachial pulse pressure amplification (PPA). Left ventricular parameters were measured with magnetic resonance imaging. Local thoracic aortic inflammation and calcification were measured by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Biomarkers of low-grade inflammation were also quantified. AoPWV was higher in elderly hypertensive subjects comparatively to normotensive controls (15.5±5.3 vs. 11.9±2.5, p=0.046), and hypertensives had a higher calcification volume. In the overall population, calcifications of the thoracic descending aorta and inflammation of the ascending aorta accounted for respectively 18.1% (p=0.01) and 9.6% (p=0.07) of AoPWV variation. Individuals with high levels of calcifications and/or inflammation had higher AoPWV (p=0.003). Inflammation had a negative effect on PPA explaining 13.8% of its variation (p<0.05). This study highlights the importance of local ascending aortic inflammation as a potential major actor in the determination of PPA while calcifications and hypertension are more linked to AoPWV. Assessment of PPA in the very elderly could provide complementary information to improve diagnostic and therapeutic strategies targeting ascending aortic inflammation.

Duration of Diabetes Predicts Aortic Pulse Wave Velocity and Vascular Events in Alström Syndrome

Context:Alström syndrome is characterized by increased risk of cardiovascular disease from childhood.Objective:To explore the association between risk factors for cardiovascular disease, aortic pulse wave velocity, and vascular events in Alström syndrome.Design:Cross-sectional analyses with 5-year follow-up.Setting:The UK NHS nationally commissioned specialist clinics for Alström syndrome.Patients:Thirty-one Alström patients undertook vascular risk assessment, cardiac studies, and aortic pulse wave velocity measurement. Subsequent clinical outcomes were recorded.Interventions:Insulin resistance was treated with lifestyle intervention and metformin, and diabetes with the addition of glitazones, glucagon-like peptide 1 agonists, and/or insulin. Thyroid and T deficiencies were corrected. Dyslipidemia was treated with statins and nicotinic acid derivatives. Cardiomyopathy was treated with standard therapy as required.Main Outcome Measures:The associations of age, gender, and risk factors for cardiovascular disease with aortic pulse wave velocity were assessed and correlated with the effects of reduction in left ventricular function. Vascular events were monitored for 5 years.Results:Aortic pulse wave velocity was positively associated with the duration of diabetes (P = .001) and inversely with left ventricular ejection fraction (P = .036). Five of the cohort with cardiovascular events had higher aortic pulse wave velocity (P = .0247), and all had long duration of diabetes.Conclusions:Duration of diabetes predicted aortic pulse wave velocity in Alström syndrome, which in turn predicted cardiovascular events. This offers hope of secondary prevention because type 2 diabetes can be delayed or reversed by lifestyle interventions.

Aging-related systemic manifestations in COPD patients and cigarette smokers.

RationaleChronic obstructive pulmonary disease (COPD) is often associated with age-related systemic abnormalities that adversely affect the prognosis. Whether these manifestations are linked to the lung alterations or are independent complications of smoking remains unclear.ObjectivesTo look for aging-related systemic manifestations and telomere shortening in COPD patients and smokers with minor lung destruction responsible for a decline in the diffusing capacity for carbon monoxide (DLCO) corrected for alveolar volume (KCO).MethodsCross-sectional study in 301 individuals (100 with COPD, 100 smokers without COPD, and 101 nonsmokers without COPD).Measurements and Main ResultsCompared to control smokers, patients with COPD had higher aortic pulse-wave velocity (PWV), lower bone mineral density (BMD) and appendicular skeletal muscle mass index (ASMMI), and shorter telomere length (TL). Insulin resistance (HOMA-IR) and glomerular filtration rate (GFR) were similar between control smokers and COPD patients. Smokers did not differ from nonsmokers for any of these parameters. However, smokers with normal spirometry but low KCO had lower ASMMI values compared to those with normal KCO. Moreover, female smokers with low KCO, had lower BMD and shorter TL compared to those with normal KCO.ConclusionsAging-related abnormalities in patients with COPD are also found in smokers with minor lung dysfunction manifesting as a KCO decrease. Decreased KCO might be useful, particularly among women, for identifying smokers at high risk for aging-related systemic manifestations and telomere shortening.

139-POS

Objectives Several studies have demonstrated an association between preeclampsia and premature development of cardiovascular disease (CVD) later in life. Although the association is incompletely understood, it probably includes pre-existing common risk factors. However, preeclampsia may also induce permanent vascular and metabolic alterations that could affect the systemic arterial elastic properties. In this regard, arterial stiffening could represent a link between the systemic effects of preeclampsia and CVD risk. We aimed to evaluate the effect of preeclampsia on markers of arterial stiffness and subclinical atherosclerosis in women with a history of preeclampsia. Methods A 10-year follow-up study comparing 19 exposed women (previous pre-eclamptic pregnancies) and 19 unexposed women (previous normotensive pregnancies) matched on age and time since delivery. Markers of arterial stiffness (aortic pulse wave velocity and augmentation index) and of atherosclerosis (carotid intima-media thickness and atheromatous plaques presence) – as well as traditional CVD risk factors - were compared between the two groups. Results Paired analysis showed a higher aortic pulse wave velocity in women with a history of preeclampsia than in unexposed women (7.96 ± 1.45 vs. 7.16 ± 0.66 m/s, respectively, P = 0.055). However, the difference fell marginally short of statistical significance. Waist-Hip ratio ( P = 0.04) and percentage with hypertension (defined as elevated systolic and/or diastolic blood pressure and/or antihypertensive drug treatment ( P = 0.03)) were significantly higher in previous preeclamptic women. No difference was observed in augmentation index, intima-media thickness or plaque presence. Conclusions Women with preeclamptic pregnancies 10 years earlier tended to have higher pulse wave velocity compared to women with previous normotensive pregnancies. To the best of our knowledge, this is the first comparative assessment of arterial stiffness 10 years after pregnancies complicated by preeclampsia. Disclosures M. Christensen: None. C.J. Kronborg: None. U.B. Knudsen: None.

Hearts and minds: linking vascular rigidity and aerobic fitness with cognitive aging

Human aging is accompanied by both vascular and cognitive changes. Although arteries throughout the body are known to become stiffer with age, this vessel hardening is believed to start at the level of the aorta and progress to other organs, including the brain. Progression of this vascular impairment may contribute to cognitive changes that arise with a similar time course during aging. Conversely, it has been proposed that regular exercise plays a protective role, attenuating the impact of age on vascular and metabolic physiology. Here, the impact of vascular degradation in the absence of disease was investigated within 2 groups of healthy younger and older adults. Age-related changes in executive function, elasticity of the aortic arch, cardiorespiratory fitness, and cerebrovascular reactivity were quantified, as well as the association between these parameters within the older group. In the cohort studied, older adults exhibited a decline in executive functions, measured as a slower performance in a modified Stroop task (1247.90 ± 204.50 vs. 898.20 ± 211.10 ms on the inhibition and/or switching component, respectively) than younger adults. Older participants also showed higher aortic pulse wave velocity (8.98 ± 3.56 vs. 3.95 ± 0.82 m/s, respectively) and lower VO2 max (29.04 ± 6.92 vs. 42.32 ± 7.31 mL O2/kg/min, respectively) than younger adults. Within the older group, faster performance of the modified Stroop task was associated with preserved aortic elasticity (lower aortic pulse wave velocity; p = 0.046) and higher cardiorespiratory fitness (VO2 max; p = 0.036). Furthermore, VO2 max was found to be negatively associated with blood oxygenation level dependent cerebrovascular reactivity to CO2 in frontal regions involved in the task (p = 0.038) but positively associated with cerebrovascular reactivity in periventricular watershed regions and within the postcentral gyrus. Overall, the results of this study support the hypothesis that cognitive status in aging is linked to vascular health, and that preservation of vessel elasticity may be one of the key mechanisms by which physical exercise helps to alleviate cognitive aging.

Mitochondrial quality control and age-associated arterial stiffening

Stiffening of large elastic arteries with age increases the risk of cardiovascular diseases (CVD), but the underlying mechanisms are incompletely understood. We investigated the role of mitochondrial quality control (QC, i.e., mitophagy and biogenesis) in arterial stiffening with aging. In C57BL6 mice, aging was associated with impaired aortic expression of mitochondrial QC mediators, greater activation of the mitochondrial redox/stress sensor p66shc, elevated superoxide production and increased arterial stiffness—as indicated by ~25% higher aortic pulse wave velocity (aPWV). In old mice, supplementation with trehalose, a nutraceutical reported to enhance mitophagy, normalized mitochondrial QC markers, p66shc activation and superoxide production, and reduced aPWV and aortic collagen I (a structural protein that confers stiffness). In vitro experiments suggested that mitochondrial QC processes were enhanced in the aortas from old trehalose-treated mice, and in aortic rings studied ex vivo, both aging and treatment with the mitochondrial stressor rotenone were associated with increases in p66shc activation and intrinsic mechanical stiffness, whereas co-incubation with trehalose prevented these effects. Taken together, these findings suggest that mitochondrial stress/dysfunction as a result of impaired mitochondrial QC contributes to large elastic artery stiffening with age. Enhancing mitochondrial QC with agents such as trehalose may be a novel strategy for reducing age-associated arterial stiffness and CVD.

Letter by Saji and Kimura Regarding Article, “Arterial Stiffness and Cerebral Small Vessel Disease: The Rotterdam Scan Study”

To the Editor: We read with great interest the article by Marielle et al1 that was recently published in Stroke . In their population-based study that included 1460 participants, increased arterial stiffness indicated by aortic pulse wave velocity (PWV), a conventional measurement of arterial stiffness, was associated with a larger volume of white matter lesions. Furthermore, lacunar infarcts and deep or infratentorial microbleeds were associated with a higher aortic PWV in persons with uncontrolled hypertension. We applaud their results, because we also showed an independent association between cerebral small vessel disease and increased arterial stiffness indicated by brachial-ankle …

Ambulatory blood pressure and subclinical cardiovascular disease in patients with juvenile-onset systemic lupus erythematosus

The aim of this study was to evaluate the presence of subclinical cardiovascular disease (CVD) and its relation to risk factors, particularly hypertension in juvenile-onset systemic lupus erythematosus (SLE). A total of 24 patients with normal renal function were examined for subclinical CVD by using non-invasive methods, including the measurement of carotid intima-media thickness (IMT), carotid distensibility, aortic pulse wave velocity (PWV) and left ventricular mass (LVM). Blood pressure (BP) pattern and the presence of hypertension were assessed by 24-h ambulatory blood pressure monitoring (ABPM). The patients had higher aortic PWV than the controls (p = 0.011). Increased carotid IMT was present in 48 % of the patients and reduced carotid distensibility in 17 %. Left ventricular hypertrophy (LVH) was present in 22 % of the patients. Eight patients were hypertensive; hypertensive patients had a significantly lower distensibility coefficient (DC)-SDS, higher aortic PWV and higher LVM index than the normotensive patients (p = 0.008, p = 0.023 and p = 0.001, respectively). Higher carotid IMT-standard deviation score (SDS) significantly correlated with higher nighttime diastolic BP-SDS (R (2) = 0.204, p = 0.046); lower DC-SDS correlated with higher nighttime systolic BP-SDS (R (2) = 0.290, p = 0.014). Increased aortic PWV was significantly associated with higher daytime systolic BP-SDS and elevated erythrocyte sedimentation rate (R (2) = 0.607, p = 0.003 and p = 0.010, respectively). PWV was the only independent predictor of LVM index (R (2) = 0.396, p = 0.004). These results provide additional evidence for the presence of subclinical CVD and its relation to hypertension in juvenile-onset SLE. They also indicate a significant relation between LVH and increased arterial stiffness. It is also important to note that our findings reveal significant relationships between ambulatory BP and cardiovascular changes and underline the importance of ABPM to predict CVD.

D-005 HIGHER POST-CHALLENGE GLUCOSE AREA UNDER CURVE SUSCEPTIBLE TO INCREASED AORTIC PULSE WAVE VELOCITY IN NON-DIABETIC HEALTHY ADULTS

Background Higher post-challenge hyperglycemia and postprandial glucose rather than fasting glucose levels have been associated with cardiovascular complications. However, the clinical association between post-challenge hyperglycemia and cardiovascular risk factors deserves more investigation. Methods During 2008–2011, we recruited patients below 60 years-old, having a formal work and without CHD, cerebrovascular, CHF, or major diseases from NTUH. This analysis was focused on the relation between aortic pulse wave velocity and the post-challenge glucose area under curve(GluAUC) after oral glucose tolerance test (OGTT) in healthy control subjects. All subjects with a fasting period of 10–14 h underwent an OGTT with 75-g of glucose loading in accordancewith the World Health Organization standard. A venous blood sample was taken before, 30, 60, 90 min, and until two hours after OGTT. The baPWV, ankle–brachial index (ABI), and 4-limbs blood pressure, measured using a noninvasive vascular screening device (Colin VP-1000; Colin Co., Ltd., Komaki, Japan), were performed for each participant. We also checked lipid profiles, including LDL and sdLDL in all subjects. Results A total of 511 control subjects without previous diagnosis of type 2 diabetes completed the study. Increasing sdLDL and GluAUC are correlated with higher aortic pulse wave velocity. Multivariate regression analysis shows that age, BMI, and SBP are strong determinants of aortic pulse wave velocity. Beyond them, LDL, sdLDL and GluAUC are also important determinants individually. Increment of 1 GluAUC leads to 0.152 ± 0.077 cm/s increment of baPWV. In higher GluAUC group (≥33 percentile), the increment is more significant (0.230 ± 0.095 cm/s). In lower GluAUC group (<33 percentile), GluAUC is not correlated with baPWV, though sdLDL still has significant correlation with baPWV. Conclusion GluAUC and sdLDL are important determinants of aortic pulse wave velocity, especially in subjects with higher GluAUC. This study was supported by grants from National Health Research Institute of Taiwan(NHRI-EX97-9721∼10021PC).