Lower Pulse Wave Velocity Research Articles

Haplotype of receptor for advanced glycation end products is associated with arterial stiffness in essential hypertension

Abstract Background What causes us to age has been extensively explored. The receptor for AGEs (RAGE) expression is up-regulated in atherosclerotic plaques and its activation leads to oxidative stress, cytokine and adhesion molecule formation, activation of nuclear factor-κB and cell apoptosis. We hypothesized that genetic variation in the RAGE receptor may be associated with arterial stiffness. Methods 309 untreated hypertensive subjects were tested for genotypes of –374T>A and –429T>C polymorphisms with polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Arterial stiffness was measured as pulse wave velocity (PWV), augmentation index (AIx) and central aortic blood pressure (BP). Data was analysed using JMP Version 13 (SAS for Windows). Results Both polymorphisms were in Hardy-Weinberg equilibrium. The –374A A allele carriers had significantly lower aortic systolic BP (143±2 vs. 154±1, p<0.001) while –429C allele carriers had lower aortic systolic BP (151±1 vs. 157±2, p<0.01) compared with T carriers. –429C allele carriers had lower PWV compared to 429TT individuals (8.86±1 vs. 10.70±2.5). –374A allele carriers had lower PWV compared to 374TT individuals (9.7±1.43 vs. 10.65±2.6). Subjects with the AC haplotype had the lowest and those with the TT haplotype the highest PWV and aortic BP than any of the other haplotypes containing one or more of the at-risk alleles. Conclusions The combined effect of the two genotypes was additive with AA homozygotes of –374T>A and C allele carriers of –429T>C and the haplotype AC, associated with lowest aortic BP and arterial stiffness. PWV & RAGE haplotypes Funding Acknowledgement Type of funding source: None

Improved nutrition in early life and pulse wave velocity and augmentation index in mid-adulthood: Follow-up of the INCAP Nutrition Supplementation Trial Longitudinal Study.

Nutrition in pregnancy and early childhood affects later blood pressure and precursors of atherosclerosis, but its influence on arterial stiffness is unexplored. This study determines whether exposure to improved nutrition during early life influences Augmentation index (AI) and pulse wave velocity (PWV) in mid-adulthood. We included 1221 adults (37-54y) who participated in a cluster-randomized nutritional supplementation trial of a protein-energy beverage (Atole), conducted between 1969–1977 in Guatemala. The comparison group received Fresco, a low-calorie protein-free beverage. In 2015–17, we measured anthropometry (weight, height, and waist-to-height ratio); AI and PWV (using carotid—femoral tonometry); blood pressure; fasting plasma glucose and serum lipids; and sociodemographic characteristics. Based on patterns of exposure, we characterized participants as fully, partially or unexposed to the intervention from conception to their second birthday (the ‘first 1000 days’). We fit pooled and sex-specific models using intention-to-treat, difference-in-difference regression analysis to test whether exposure to the supplement in the first 1000 days was associated with AI and PWV in adulthood adjusting for basal and current sociodemographic variables and current life-style and cardio-metabolic risk factors. Prevalence of obesity in men and women was 39.6% and 19.6%, and prevalence of hypertension was 44.0% and 36.0%, respectively. Women had higher AI (34.4±9.6%) compared to men (23.0± 9.8%), but had similar PWV (7.60±1.13 m/s and 7.60±1.31, respectively). AI did not differ significantly across intervention groups. PWV was lower in individuals with full exposure to the supplement during the first 1000 days (-0.39m/s, 95% CI -0.87, 0.09; p = 0.1) compared to unexposed individuals. This difference was similar after adjusting for cardio-metabolic risk factors (-0.45m/s; 95%C-0.93, 0.01; p = 0.06). Exposure to improved nutrition during the first 1000 days was marginally associated with lower PWV, but not with AI.

Abstract 14: Glyburide Treatment Improves Aortic Arch Pulse Wave Velocity In A Murine Model Of Alzheimer’S Disease

Brain hyperexcitability is a defining feature of AD, where aberrant neuronal activity may be both a cause and consequence of the pathology. Identifying novel targets to modulate cellular excitability is an important treatment strategy. We showed that inward rectifying, ATP-sensitive potassium (K ATP ) channels regulate excitability at the neurovascular unit to impact production and aggregation of amyloid-beta (Aβ), a hallmark of AD. Sulfonylureas such as glyburide (GLY) are antidiabetic medications that inhibit K ATP channels. We demonstrated that systemic treatment with GLY decreased Aβ production and plaque pathology by modulating vascular K ATP channel activity and neuronal excitability. Here, we investigated whether GLY alters cardiac function or pulse wave velocity (PWV) in APPswe, PSEN1dE9 (APP/PS1) mice, a model of Aβ overexpression.Female APP/PS1 mice at 8 months of age with established amyloid plaque pathology were treated for 1 month with GLY (subcutaneous, slow release 2.5mg pellet, ~30μg/GLY/day) or Placebo (n = 5, each group). After 1 month, transthoracic echocardiography was performed (Vevo 2100 LAZR, FUJIFILM/VisualSonics, Inc.; Toronto, Ca) with a 30 MHz linear array transducer. There were no differences in Placebo vs. GLY mice for heart rate, cardiac output, E/e’ ratio, ejection fraction, and fractional shortening. Arterial stiffness, measured as PWV in the aortic arch [Distance (D)/Time (T); D = mm from ascending to descending aorta and T = (R to ascending aorta foot) - (R to descending aorta foot) in ms], was lower in GLY treated mice (5 ± 1 vs. Placebo 9 ± 1 mm/ms; p < 0.04). Wild Type females at 9 months of age (n = 5) reveal similar cardiac function values as Placebo and GLY treated APP/PS1 mice, with a trend for lower PWV (6 ± 1 mm/ms) than the APP/PSI Placebo group. Thus, short-term treatment with GLY does not impact overall cardiac function. Moreover, improved vascular stiffness in GLY-treated APP/PS1 mice may contribute to improved neurovascular coupling independent of changes in Aβ aggregation, since arterial stiffness is associated with increased cerebrovascular pathology in clinical studies. SLM: Bright Focus Fdn, NIA K01AG050719, Donors Cure New Vision; SMD: T32AA007565; Hypertension & Vasc Res Ctr; NCATS UL1TR001420 (Vevo Core)

Arterial stiffness and microvascular disease in type 2 diabetes.

The clustering of arterial stiffness with microvascular disease (MD) and their effects on the clinical outcome of patients with type 2 diabetes (T2D) remains not fully clarified. In a prospective study of 414 patients with T2D, we investigated the prognostic value of arterial stiffness and MD for clinical outcomes. Participants were assessed for the presence of MD (ie diabetic retinopathy, nephropathy and neuropathy) and arterial stiffness by pulse wave velocity (PWV) and followed-up for a median of 30 (range 1-60) months. The primary endpoint of the study was the composite endpoint of major adverse cardiovascular events, that is, cardiovascular and non-cardiovascular mortality and non-fatal myocardial infarction/stroke. A total of 146 (35.3%) patients had evidence of MD at baseline. In cox regression models, MD and PWV were independently associated with the composite clinical endpoint; for MD hazard ratio (HR), 3.24, 95%CI, 1.10-9.54, P=.032, and for PWV HR, 1.20, 95%CI, 1.06-1.36, P=.004) after adjustment for traditional risk factors, and enhanced risk discrimination and reclassification. The subgroup of patients with MD and high PWV was associated with increased incidence of the composite clinical endpoint (20.9% vs 1.8% in those with no MD & low PWV, P=.001). Importantly, absence of MD at baseline was associated with no mortality events during the follow-up period. PWV at baseline was not associated with MD progression during follow-up. These findings support that screening for arterial stiffness and MD in the routine clinical assessment of patients with T2D may enhance prognostication and cardiovascular risk reclassification.

Ethnic differences in subclinical vascular function in South Asians, Whites, and African Americans in the United States.

BackgroundSouth Asians are a high-risk ethnic group for cardiovascular disease despite having lower levels of conventional cardiovascular risk factors such as obesity and smoking. Ethnic differences in pulse wave reflections, arterial stiffness, and subclinical atherosclerosis as measured using augmentation index (AIX), pulse wave velocity (PWV), and carotid intima-media thickness (CIMT) may reflect some of this excess risk.MethodsWe conducted a cross-sectional analysis of pooled data from three community-based sources in Atlanta, Georgia, USA. Data on 530 South Asians collected from local health fairs was compared with data on 507 White and 192 African Americans from the Emory Predictive Health Initiative and 351 White and 382 African Americans from the Morehouse and Emory Team up to Eliminate Health Disparities Study.ResultsLinear regression models adjusted for age, sex, smoking, MAP, fasting glucose, TC, HDL-C, creatinine, and body mass index were used to assess the relationship between ethnicity and vascular function measures. In fully adjusted models, South Asians had higher heart rate corrected AIX as compared with Whites and African Americans (by 5.47%, p < 0.01 and 3.50%, p < 0.01; respectively), but lower PWV (by 0.51 m/s, p < 0.01 and 0.72 m/s, p < 0.01; respectively) and lower CIMT (by 0.02 mm p = 0.03 and 0.04 mm p < 0.01; respectively).ConclusionsSystemic pulse wave reflections, independent of other risk factors, are higher in South Asians as compared with Whites and African Americans. Future research is needed to determine whether higher AIX explains the increased cardiovascular risk among South Asians.

Incremental prognostic value of aortic stiffness in addition to myocardial ischemia by cardiac magnetic resonance imaging

BackgroundAortic stiffness is an independent predictor of cardiovascular (CV) events and mortality. However, no data exists for the prognosis of combined aortic stiffness and myocardial ischemia. Using cardiac magnetic resonance (CMR) imaging, we assessed the association of aortic stiffness by pulse wave velocity (PWV), myocardial ischemia, and CV events in patients with known or suspected coronary artery disease (CAD).MethodsVelocity-encoded CMR was performed in 520 patients who had undergone adenosine stress CMR. The PWV was determined between the mid-ascending and mid-descending thoracic aorta. Patients were divided into 4 groups by PWV (higher or lower PWV) and myocardial ischemia (positive or negative ischemia). Combined CV events including mortality, acute coronary syndrome, heart failure, coronary revascularization, and stroke were analyzed among the 4 groups.ResultsThe median follow-up period was 46.5 months, and the median PWV was 10.54 m/sec. Myocardial ischemia was positive in 199 patients (38.3%). The group with a higher PWV and positive ischemia had the most CV events (hazard ratio 8.94, p < 0.001). The group with a higher PWV and negative ischemia also was significantly associated with CV events (HR 2.19, p = 0.02). Groups with a lower PWV-positive ischemia and a higher PWV-negative ischemia showed no difference in terms of CV events (HR 0.60, p = 0.08). Patients with myocardial ischemia who had higher PWV demonstrated significantly higher event rates than those who had lower PWV (HR 2.41, p < 0.001). Multivariate analysis demonstrated that myocardial ischemia and PWV were independent predictors for combined CV events (HR 2.71, p < 0.001 and HR 2.42, p < 0.001, respectively).ConclusionsStress perfusion CMR provided prognostic utility in patients with known or suspected CAD. Adding aortic stiffness to stress perfusion CMR could improve risk assessment and prediction for future CV events.

P1270INCREASED SCLEROSTIN, BUT NOT DKK-1 PROTEIN, IS ASSOCIATED WITH ELEVATED PULSE WAVE VELOCITY IN HEMODIALYSIS SUBJECTS

Abstract Background and Aims Sclerostin and Dickkopf-1 (Dkk-1) protein are inhibitors of the canonical Wnt/β-catenin bone pathway. Pilot data suggest that sclerostin may be involved in vascular changes in CKD, but data on Dkk-1 effects are scarce. This is the first study investigating simultaneously the associations of sclerostin and Dkk-1 with arterial stiffness in hemodialysis patients. Method 80 patients on chronic hemodialysis had carotid-femoral pulse wave velocity (PWV), central BP and wave reflections evaluated with applanation tonometry (Sphygmocor) in a mid-week non-dialysis day. Serum levels of sclerostin and Dkk-1 were measured with ELISA. A large set of demographic, co-morbid, laboratory and drug parameters were used in the analyses. Results Subjects with PWV&amp;gt;9.5 m/sec (high arterial stiffness group, n=40) were older, had higher BMI, higher prevalence of hypertension, diabetes and coronary-heart-disease and higher peripheral SBP, central SBP, C- reactive protein and serum sclerostin (p=0.02), but similar Dkk-1 compared to subjects with low PWV. When dichotomizing the population by sclerostin levels, those with high sclerostin had higher PWV than patients with low sclerostin levels (10.63±2.71 vs 9.77±3.13, p=0.048). Increased sclerostin (&amp;gt;200 pg/ml) was significantly associated with increased PWV (&amp;gt;9.5 m/s) (HR:2.778, 95%CI:1.123-6.868, per pg/ml increase); this association remained significant after stepwise adjustment for Dkk-1, iPTH and calcium x phosphate product. In contrast, no association was noted between Dkk-1 and PWV (HR: 1.000, 95%CI: 0.416-2.403). Conclusion Serum sclerostin is associated with PWV independently of routine markers of CKD-MBD in hemodialysis patients. In contrast Dkk-1 has no association with arterial stiffness and is rather not pathophysiologically involved in relevant vascular changes.

Abstract P519: Multivitamin Use And Arterial Stiffness In Older Women And Men

Introduction: A multivitamin (MV) is the most commonly taken supplement in older U.S. adults. Arterial stiffness is an important intermediate marker of cardiovascular disease (CVD). However, few studies have examined the association of MV use and arterial stiffness. Hypothesis: Regular multivitamin use is associated with lower levels of arterial stiffness. Methods: A subcohort of participants enrolled in the COcoa Supplement and Multivitamin Outcomes Study (COSMOS), a large scale randomized clinical trial testing a MV and a cocoa extract supplement on CVD and cancer, completed baseline measurement of arterial stiffness assessed by pulse wave velocity (PWV), augmentation index (AI), and central blood pressure (CBP). Frequency and duration of MV use was assessed via self-report questionnaire at baseline. The cross-sectional association of MV use and arterial stiffness was evaluated by multivariate linear regression with adjustment for conventional CVD risk factors. We also performed subgroup analyses to evaluate effect modification between MV use and sex, age, body mass index (BMI), and hypertension. Results: A total of 470 (229 women and 241 men) COSMOS participants were included in this study, with mean age 69.1±5.2 years, of whom 150 (32%) reported current MV use at baseline. Multivariate linear regression analysis revealed that current MV use (yes versus no) was significantly associated with lower PWV (β:-0.59±1.02, p=0.004) but not associated with other measures of arterial stiffness, including AI or CBP. There were also no consistent associations between frequency and duration of MV use with any of the measures of arterial stiffness. Also, there was no effect modification by sex, age, BMI, or hypertension on the association between MV use and arterial stiffness. Conclusions: MV use was associated with lower PWV in older subjects. Further results from the COSMOS trial on randomized MV supplementation and changes in arterial stiffness over 2 years will further elucidate the effects of MV on arterial stiffness.

Abstract P133: Circulating Anti-Müllerian Hormone and Subclinical Cardiovascular Disease in Middle-aged and Older Men

Introduction: Anti-Müllerian hormone (AMH) is primarily known for its role in sexual differentiation during embryogenesis, and ovarian follicle development in premenopausal women. Furthermore, recent research suggests that higher AMH levels are associated with a lower occurrence of (subclinical) cardiovascular disease (CVD) in both women and men. However, these studies only included a small variety of subclinical CVD measures. We aimed to investigate whether circulating AMH is associated with a wider range of subclinical CVD measures in middle-aged and older men. Hypothesis: Higher AMH levels are associated with more favorable levels of subclinical CVD measures. Methods: We analyzed data from 371 male participants (aged 40-80 years at recruitment) from a Dutch population-based study. AMH was measured in serum samples obtained at recruitment using the Elecsys ® AMH assay (Roche Diagnostics). At baseline we measured carotid intima-media thickness (cIMT)(μm), pulse wave velocity (PWV)(m/s) and aorta diameter (cm), and calculated Framingham risk score predictions. We investigated associations between AMH (μg/L) levels, both continuously and in tertiles, and these outcomes using linear regression models adjusted for known CVD risk factors, free testosterone, free estradiol and dihydroepiandrosterone sulphate (DHEAS). Sensitivity analyses comprised exclusion of prevalent diabetes and CVD cases. Results: Higher AMH levels were associated with a lower cIMT at baseline (β continuousAMH = -6.3, 95%CI: -10.7, -1.9; β T2vsT1 = -30.6, 95%CI: -60.2, -0.9; β T3vsT1 = -39.8, 95%CI: -70.1, -9.6). We observed no statistically significant associations between AMH and the remaining outcomes, but effect estimates indicated that higher AMH levels may be associated with lower PWV (β continuousAMH = -0.02, 95%CI: -0.10, 0.05), and lower Framingham risk score predictions (β continuousAMH = -0.004, 95%CI: -0.008, 0.000). Exclusion of prevalent diabetes and CVD cases did not change our conclusions. Conclusions: The results of this study suggest that higher AMH levels are associated with a lower cIMT in middle-aged and older men. Based on our results we cannot exclude a possible relation between circulating AMH levels and other measures of subclinical cardiovascular disease.

Predictive value of the combination of brachial-ankle pulse wave velocity and ankle-brachial index for cardiovascular outcomes in patients with acute myocardial infarction.

Although ankle-brachial index and brachial-ankle pulse wave velocity measurement are well-established modalities for assessing peripheral artery disease and arterial stiffness and predicting cardiovascular events, it is unclear which one is more important or if a combination of the two is more effective for determining prognosis among patients with acute myocardial infarction. Patients with acute myocardial infarction (n = 889) were stratified into four groups according to a brachial-ankle pulse wave velocity (cut-off value: 1684 cm/s) and ankle-brachial index (cut-off value: 0.98): group I (high ankle-brachial index and low brachial-ankle pulse wave velocity, n = 389), group II (high ankle-brachial index and high brachial-ankle pulse wave velocity, n = 281), group III (low ankle-brachial index and low brachial-ankle pulse wave velocity, n = 103), group IV (low ankle-brachial index and high brachial-ankle pulse wave velocity, n = 116). The mean follow-up duration was 348 days. Major adverse cardiovascular events or cardiac death occurred in 64 (7.2%) and 26 patients (2.9%), respectively. In multivariable analysis, group III and IV had a significant high hazard ratio for major adverse cardiovascular events (5.93, 5.43) and cardiac death (13.51, 19.06). Additionally, ankle-brachial index had a higher hazard ratio than brachial-ankle pulse wave velocity for major adverse cardiovascular events (3.38 vs. 1.40) and cardiac death (6.21 vs. 2.40). When comparing receiver operating characteristic curves of the combined models of risk factors, brachial-ankle pulse wave velocity, and ankle-brachial index, pulse wave velocity plus ankle-brachial index or pulse wave velocity plus ankle-brachial index plus risk factors were significantly more predictive of major adverse cardiovascular events than risk factors. Our findings indicate that ankle-brachial index is a strong independent prognostic factor and adding a brachial-ankle pulse wave velocity measurement to ankle-brachial index increases the prognostic power for cardiac events in patients with acute myocardial infarction, while ankle-brachial index and pulse wave velocity showed additive value to risk factors.

SUN-015 VASCULAR STIFFNESS AS A PREDICTOR OF ACUTE KIDNEY INJURY FOLLOWING CABG – A PILOT STUDY

AKI following coronary artery bypass graft (CABG) is common, potentially preventable but there is no accepted method to identify those at risk. Arterial stiffness is a predictor of CVD, renal disease and stroke. This study examined arterial stiffness, assessed by pulse wave velocity, as a predictor of AKI post CABG surgery. The study recruited 63 patients (18-80 years) undergoing isolated elective CABG. Anthropometric variables, renal function and pulse wave velocity (PWV) were measured pre-operatively and renal function was assessed post-operatively for 5 days. Aortic tissue samples were obtained intra-operatively and were histologically analysed. AKI staging was based on the KDIGO definition. Statistical analysis was obtained using SPSS 25. Ethical approval for this study was granted by NRES Surrey Research Ethics committee. Baseline characteristics are as shown in table 1. Seven patients (11%) of patients developed AKI stage 1 following surgery. PWV was higher in patients who developed AKI compared to those who did not (12.2 ± 3.5 vs 9.9 ± 2.6 m/s; p=0.045). PWV increased with age (Pearson correlation 0.519; p=0.000) and was higher in diabetic patients (12.4 ± 2.5 vs 9.3 ± 2.4; p= 0.000). PWV was also high with high systolic BP, ≥140mmHg, (11.5 ± 2.5 vs 9.3 ± 2.6; p=0.001). Histological comparison of aortic samples of an AKI patient with high PWV compared to a non- AKI patient with low PWV (Figure 1) shows differences in calcification and elastin. PWV was higher in patients who developed AKI following CABG. The PWV was also higher in CABG patients with diabetes, older age and sBP. Further study will be needed with more patients to establish a link.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Exercise and Arterial Stiffness in the Elderly: A Combined Cross-Sectional and Randomized Controlled Trial (EXAMIN AGE).

Introduction:Arterial stiffness (AST) is a main determinant of cardiovascular (CV) mortality. Long-term physical activity (PA) is considered to decrease age-related progression of AST but effects of short-term exercise interventions on AST remain unclear.Methods:In a combined cross-sectional and interventional study approach, we investigated the effects of long-term PA and short-term high-intensity interval training (HIIT) on AST in an older population. 147 older individuals (mean age 59 ± 7 years) were assigned to three groups according to their PA and CV risk profile and compared: healthy active (HA, n = 35), healthy sedentary (HS, n = 33) and sedentary at risk (SR, n = 79). In addition, SR were randomized to either 12 weeks of HIIT or standard recommendations. Pulse wave velocity (PWV) was measured by applanation tonometry. Cardiorespiratory fitness (CRF) was performed by symptom-limited spiroergometry to determine maximal oxygen uptake (VO2max).Results:Higher CRF was associated with lower PWV (p < 0.001) and VO2max explained 18% of PWV variance. PWV was higher in SR (8.2 ± 1.4 m/s) compared to HS (7.5 ± 1.6 m/s) and HA (7.0 ± 1.1 m/s; p < 0.001). 12 weeks of HIIT did not change PWV in SR. HIIT-induced reduction in systolic BP was associated with a reduction in PWV (p < 0.05).Discussion:SR show higher PWV compared to HS and long-term PA is associated with lower PWV. Reduction of AST following short-term HIIT seems to depend on a concomitant decrease in blood pressure. Our study puts into perspective the effects of long- and short-term exercise on arterial wall integrity as treatment options for CV prevention in an older population.Clinical Trial Registration:ClinicalTrials.gov: NCT02796976 (https://clinicaltrials.gov/ct2/show/NCT02796976).

Abstract P3007: Effect of Anti-Hypertensive Treatment Lisinopril on Central Arterial Stiffness and Anxiety-Like Behavior in Adult Hypertensive Dahl Salt-Sensitive Rats

Background: Independent of a high salt intake, Dahl Salt-Sensitive (DSS) rats demonstrate an age-associated increase in blood pressure (BP), and central arterial stiffness estimated by pulse wave velocity (PWV) accompanied by cognitive decline. We hypothesized, that anti-hypertensive treatment Lisinopril, in addition to BP decrease, will lower PWV and improve cognition of adult DSS. Methods: Twenty 6-mo old male DSS were kept on normal salt diet for the duration of the study; ten of them were continuously treated with Lisinopril (15 mg/kg/day) for 3 months. Systolic BP (SBP) and PWV (by doppler echocardiography) were measured, and open field test (OFT) was performed to assess locomotor and anxiety-like behavior at baseline prior to treatment and repeated in 3 months in 9-mo old rats. In a sub-cohort of DSS rats SBP was measured in 3-mo-old DSS. The data are presented as mean ± standard deviation and analyzed by 2-way ANOVA and T-test. Results: Prior to treatment, all DSS rats displayed hypertension and BP elevation with age (SBP: 170±11 vs. 142±5 mmHg, 6-mo vs. 3-mo; P&lt;0.01). After 3 months, control untreated animals showed no difference in SBP and were hypertensive. Rats treated with Lisinopril for 3 months showed a decreased SBP (119±9 vs. 171±11 mmHg, P&lt;0.0001) and a decreased PWV compared to their baseline prior to treatment (3.03±1.23 vs. 5.52±1.07 m/s p&lt;0.05). In OFT, treatment with Lisinopril increased exploration of the center of the field compared to the control group (120±35 vs. 87±30% of distance traveled in center to baseline , p=0.05) without affecting total distance traveled, indicating a reduction in anxiety-like behavior. Conclusion: Lowering of BP and PWV is associated with reduced anxiety-like behavior in DSS, which indicate the connection of cardiovascular disorder and cognitive function in adult hypertensive DSS. Whether Lisinopril has an additional direct effect on brain structure and function in DSS rats will be further studied. This research was supported entirely by the Intramural research Program of the NIH, National institute on Aging

Abstract P112: Sex Differences and the Role of G Protein-Coupled Estrogen Receptor in Arterial Stiffening

Pulse wave velocity (PWV) independently predicts cardiovascular events and is exacerbated in women following menopause. Since our previous work shows that G protein-coupled estrogen receptor (GPER) plays a protective role in the vasculature, the current study evaluated sex differences and the impact of GPER on arterial stiffening. We hypothesized that genetic deletion of GPER attenuates sex differences in arterial stiffness. Male and female wildtype (wt) and global GPER knockout (ko) mice (n=46) were used between 16-21 weeks of age. Ang II infusion (700 ng/kg/day for two weeks) was used to induce hypertension, and SBP was measured using tail cuff plethysmography. Local PWV within the carotid artery was obtained via high frequency ultrasound in both color Doppler and M-mode. The excised carotid was subjected to passive biaxial mechanical testing followed by four fiber family constitutive modeling. Statistical analysis was performed using two-way ANOVA with Sidak’s multiple comparisons test. Baseline SBP was significantly lower in females (P=0.035) but was not impacted by genotype. Baseline PWV was significantly higher in male versus female wt mice (P&lt;0.01) but was not different in ko mice. Baseline axial (P&lt;0.01) and circumferential (P=0.027) stiffness was higher in female wt mice but was not impacted by genotype. Ang II infusion significantly increased SBP (P&lt;0.001) and PWV (P&lt;0.001) in all groups, removing any impact of sex or genotype. Ang II increased axial stiffness and decreased diagonal collagen in male and female GPER ko mice. In conclusion, we found that GPER deletion did not impact blood pressure but removed sex differences in PWV. While female wt mice had the lowest PWV at baseline, genetic deletion of GPER or Ang II infusion removed this protection independent of BP. Therefore, local carotid PWV may provide information on vascular status independent of BP, and GPER plays an important role in vascular compliance and arterial stiffening.

Association of non-invasive measures of subclinical atherosclerosis and arterial stiffness with mortality and major cardiovascular events in chronic kidney disease: systematic review and meta-analysis of cohort studies.

BackgroundNon-invasive cardiovascular disease (CVD) risk prediction, in subclinical stages, aiming to stratify patients and tailor interventions remains an unmet need in chronic kidney disease (CKD). In this meta-analysis, we summarize the association of carotid intima–media thickness (cIMT), coronary artery calcium score (CACS) and pulse wave velocity (PWV) with all-cause mortality, cardiovascular (CV) mortality and CV events in non-dialysis CKD and patients on haemodialysis.MethodsSystematic review and meta-analysis of prospective cohort studies.ResultsOut of 27 984 records, a total of 45 studies were eligible for quantitative synthesis; 11 for cIMT, 18 for CACS and 16 for PWV involving 2235, 4904 and 5717 patients, respectively. Meta-analysis was possible from pooled data of five cIMT studies (708 subjects), eight CACS studies (862 subjects) and nine PWV studies (1508 subjects). In dialysis patients, cIMT was associated with all-cause mortality [relative risk (RR) per unit increase: 1.08, 95% confidence interval (CI) 1.00–1.17, I2: 68%] and CV mortality (RR: 1.29, 95% CI 1.14–1.47, I2: 0%). High versus low CACS was associated with all-cause mortality (RR: 2.51, 95% CI 1.66–3.79, I2: 5.7%) and CV events (RR: 3.77 95% CI 2.16–6.58, I2: 20.2%). High versus low PWV was associated with all-cause (RR: 5.34, 95% CI 3.01–9.47, I2: 0%) and CV mortality (RR: 8.55, 95% CI 4.37–16.73, I2: 0%). The combined estimated for all-cause mortality per 1 m/s increment unit in PWV was 1.25 (95% CI 1.17–1.34, I2: 0%) and for CV mortality was 1.24 (95% CI 1.16–1.34, I2: 15.5%). In non-dialysis patients, CACS was associated with CV events (RR: 4.02, 95% CI 1.57–10.29, I2: 63.4%). High versus low PWV was associated with all-cause mortality (RR: 2.52, 95% CI 1.40–4.55, I2: 62.6%).ConclusionsNon-invasive measures of atherosclerosis and arterial stiffening are associated with all-cause and CV mortality as well as CV events among patients with all stages of CKD. These markers could be considered for the evaluation of CV morbidity and mortality risks. Moreover, the results of this meta-analysis support the study of interventions, with effect on these markers of vascular disease, on long-term CVD outcomes.

A Low Ankle-Brachial Index and High Brachial-Ankle Pulse Wave Velocity Are Associated with Poor Cognitive Function in Patients Undergoing Hemodialysis.

Patients with end-stage renal disease (ESRD) have an increased risk of both impaired cognitive function and peripheral artery disease (PAD) than the general population. The association between PAD and dementia is recognized, but there are limited studies in patients with ESRD. The aim of this study was to evaluate the relationship between ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) and cognitive impairment in patients receiving hemodialysis (HD). We enrolled 136 prevalent HD patients (mean age 59.3 ± 10.5 years, 55.9% male). Cognitive performance was measured using the Montreal Cognitive Assessment (MoCA) and Cognitive Abilities Screening Instrument (CASI) by trained psychiatrists. Associations between the cognitive function and ABI and baPWV were assessed using multiple linear regression analysis. Compared with HD patients with ABI ≥ 0.9, patients with ABI < 0.9 had lower MoCA score (p = 0.027) and lower CASI score but did not achieve significant level (p = 0.056). In the multivariate stepwise linear regression analysis, ABI (per 0.1) was independently positively associated with the MoCA score (β coefficient = 0.62, p = 0.011) and the CASI score (β coefficient = 1.43, p = 0.026). There is a negative association between baPWV (per 100 cm/s) and CASI (β coefficient = −0.70, p = 0.009). In conclusion, a low ABI or high baPWV was associated with a lower cognitive function in HD patients.

EVALUATION OF BLOOD PRESSURE AND PULSE WAVE VELOCITY IN HEALTHY YOUTHS WITH/WITHOUT SPORTS CUSTOMS

Objective: Pulse Wave Velocity (PWV) was an examination to measure the level of atherosclelosis. Previous report showed that risk factor of atherosclelosis as hypertension, diabetes mellitus, hyperlipidemia, aging, smoking made PWV faster. On other studies, PWV in non-smoking youths were associated with obese and hyperlipidemia (Intern Med. 2005; 44:696–701.). Aim: Correlation PWV with other risk factors were not elucidated. In this study, first, we featured to the relationship between PWV and Familial History (FH) and Blood Pressure (BP) in Healthy, non-smoking youths without abnormal data of blood test in medical examination (blood sugar, lipid, liver and renal function). And next, we paid attention to the difference in risk mitigation due to the presence or absence of sports customs. Design and method: Non-smoking healthy youths,72 men and 30 women with chance sports customs (CSC), 36 men and 15 women with daily sports customs (DSC), without abnormal data of blood test in medical examination was entry in this study. If he or she had a familial history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease, cerebrovascular disease in father or mother, it counted as two point, and also in grandfather or grandmother, as one point by each risk factor. And in this study, called three former risk factors as “disease risk (DR)”, two latter risk factors as “outbreak risk (OR)”. Results: Mean PWV was faster in men and women with CSC than those with DSC. Next we sort these data into ascending-order, and devided into “low PWV (LP)” and “high PWV (HP)” bound on the median. Both PWV of Men and women recorded HP is faster than recorded LP with CSC and DSC, however in BP, both Men and women recorded HP is faster than recorded LP with CSC but these difference in men and women with DSC has tendency to shirink statistically. Conclusions: We conclude that familial history and BP may correlate with PWV in healthy youths with chance sports customs especially in HP. But daily sports customs pretend to rise their BP.

Arterial stiffness relates to executive dysfunction in later life

ABSTRACTCardiovascular disease in older people is often linked with cognitive impairment, particularly in domains of executive function and processing speed. Our aims examined whether carotid-femoral pulse wave velocity (PWV) related to subtle changes of executive function and processing speed. Fifty-six individuals with subjective mood and/or cognitive concerns underwent PWV and neuropsychological assessments of processing speed (Trail Making Test Part A) and executive functioning (Delis Kaplan Executive Function System Stroop Task; Trail Making Test Part B, TMT-B). Individuals with high PWV (≥12.0m/s) had poorer performance on TMT-B, compared to low PWV (<12.0m/s), and a moderate negative correlation (r = −0.38, p = .004) between PWV and TMT-B performance. Our results confirm that in older adults at-risk for cognitive decline, early markers of CVD are associated with subtle decrements in rapid set-shifting (executive function), supporting efforts towards early detection of CVD as a secondary prevention strategy for older individuals with cognitive decline.

In vivo characterization of doxycycline-mediated protection of aortic function and structure in a mouse model of Marfan syndrome-associated aortic aneurysm

Aortic aneurysm is the most life-threatening complication in Marfan syndrome (MFS) patients. Doxycycline, a nonselective matrix metalloproteinases inhibitor, was reported to improve the contractile function and elastic fiber structure and organization in a Marfan mouse aorta using ex vivo small chamber myography. In this study, we assessed the hypothesis that a long-term treatment with doxycycline would reduce aortic root growth, improve aortic wall elasticity as measured by pulse wave velocity, and improve the ultrastructure of elastic fiber in the mouse model of MFS. In our study, longitudinal measurements of aortic root diameters using high-resolution ultrasound imaging display significantly decreased aortic root diameters and lower pulse wave velocity in doxycycline-treated Marfan mice starting at 6 months as compared to their non-treated MFS counterparts. In addition, at the ultrastructural level, our data show that long-term doxycycline treatment corrects the irregularities of elastic fibers within the aortic wall of Marfan mice to the levels similar to those observed in control subjects. Our findings underscore the key role of matrix metalloproteinases during the progression of aortic aneurysm, and provide new insights into the potential therapeutic value of doxycycline in blocking MFS-associated aortic aneurysm.

Steps per Day and Arterial Stiffness.

Arterial stiffness has emerged as an independent predictor of cardiovascular morbidity and mortality. Furthermore, objectively monitored steps per day is widely perceived to be beneficial for controlling health risk factors, and for preventing morbidity and mortality. The aim of this review was to determine the relationship between steps per day and arterial stiffness, as measured by its reference standard, pulse wave velocity (PWv). We systematically searched for cross-sectional data from studies addressing the association between steps per day and PWv. The DerSimonian and Laird method was used to compute pooled estimates of correlation and their respective 95% CI. Additionally, we used a regression model to estimate the pooled mean PWv by categories of physical activity behavior: sedentary <5000; low active 5000 to 7499; active 7500 to 9999; and highly active 10 000+. Twenty published studies were included in the systematic review, but only 10 studies in adults and older adults could be incorporated in the meta-analysis. Steps per day was inversely correlated with arterial stiffness measured by PWv in adults and older adults (r=-0.18; 95% CI: -0.27 to -0.10; P<0.001), with substantial heterogeneity ( I2=77.9%; P<0.001). The regression model showed that the pooled PWv was lower with a corresponding higher level of steps per day, influenced primarily by low PWv values for the highly active lifestyle category ( Ptrend=0.005). This systematic review and meta-analysis demonstrates a clinically meaningful association between objectively monitored steps per day and PWv, an accepted indicator of arterial stiffness and an early subclinical risk factor for cardiovascular disease. Systematic Review Registration- PROSPERO CRD42018088228.