Abstract P285: Aging In Male Mice Is Characterized By Arterial Stiffening And Diastolic Dysfunction

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Benard O Ogola ◽  
Bruna Visniauskas ◽  
Isabella Kilanowski-doroh ◽  
Caleb M Abshire ◽  
Alec Horton ◽  
...  

Aging is a nonmodifiable risk factor for cardiovascular mortality and is associated with arterial stiffening and cardiac dysfunction. In this study, we hypothesized that aging would decrease vascular compliance and cardiac function in male mice. Tail-cuff plethysmography was used to measure blood pressure, pulse wave velocity (PWV) for arterial stiffness, echocardiography for systolic and diastolic cardiac function, and wire myography for vessel reactivity in mature adult (25 weeks) and middle-aged (57 weeks) C57Bl/6 mice. Data was analyzed by t-test or 2-way ANOVA, and P<0.05 was considered significant. While there was no difference in blood pressure, PWV was higher in middle-aged male mice (1.8 ± 0.04 m/s vs. 1.2 ± 0.05 m/s; P<0.001) and associated with increased left ventricular (LV) posterior wall thickness (1.4 ± 0.07 mm vs. 1.1 ± 0.13 mm; P=0.03), and LV mass (172 ± 8 mg vs. 158 ± 20 mg; P=0.04). The ratio of early to late filling velocities, a measure of diastolic function, was lower in middle-age (1.6 ± 0.07 vs. 2.7 ± 0.37; P<0.001). Carotid artery histological analysis indicated that middle-aged mice had a greater collagen-to-elastin ratio along with decreased amounts of smooth muscle and thin collagen (P<0.05). Mesenteric artery contraction to PGF2α (446 ± 15% vs. 378 ± 14%; P=0.02) as well as relaxation to sodium nitroprusside (55 ± 7% vs. 31 ± 7%; P<0.01) were both blunted in the middle-aged group. The current study demonstrates that aging in male mice increases arterial stiffening and LV remodeling while decreasing diastolic and vascular function, independent of increased blood pressure. Future studies will investigate whether strategies that counteract arterial stiffness in the absence of changes in blood pressure can protect from cardiovascular aging.

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Sarah Johnson ◽  
Nicole Litwin ◽  
Hannah Van Ark ◽  
Shannon Hartley ◽  
Emily Fischer ◽  
...  

Abstract Objectives The gut microbiota is emerging as an important regulator of cardiovascular health. Indeed, gut dysbiosis is increasingly being linked to the development of cardiovascular disease (CVD). Aging and obesity are associated with the development of CVD largely due to the development of vascular dysfunction, namely endothelial dysfunction and arterial stiffness. The objective of this study was to examine the relationship between the gut microbiota, blood pressure, and vascular function in aging overweight and obese individuals. Methods This cross-sectional study included fifteen overweight and obese (mean body mass index, BMI: 29.5; range: 25.8–37.0) middle-aged/older men and postmenopausal women (mean age: 53; range: 42–64 years). Blood pressure, arterial stiffness (augmentation index, AIx, and aortic pulse wave velocity, aPWV), and endothelial function (reactive hyperemia index, RHI) were assessed. Stool samples were collected for gut microbiota analysis using 16S ribosomal RNA sequencing. Principal coordinates analysis and Pearson's correlations were performed to evaluate the relationship between the gut microbiota and measures of vascular function and blood pressure. Results Global gut microbiota phenotypes clustered most strongly by aPWV (groups separated by median value) as visualized by Non-Metric Dimensional Scaling plot of Bray-Curtis Distances (stress = 0.09; P = 0.07). Several bacterial taxa correlated with vascular parameters. For example, Bifidobacterium longum (r = 0.80, P < 0.001) and Akkermansia muciniphila (r = 0.56, P = 0.047) were positively correlated with RHI. Bifdobacterium bifidum (r = −0.61, P = 0.02) and Oxalobacter formigenes (r = −0.62, P = 0.02) were negatively correlated with systolic blood pressure. Interestingly, there was no significant clustering by BMI groupings (overweight vs. obese) or correlations between BMI and specific taxa. Conclusions These preliminary data suggest that the gut microbiota is linked to vascular dysfunction and increased blood pressure in aging overweight and obese individuals independent of BMI. Further data collection and analysis are currently underway to explore these relationships in a larger human cohort, and to explore underlying mechanisms through transferring of vascular phenotypes in humans to germ-free mice through microbiota transplantation. Funding Sources NIFA, USDA.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Kalos ◽  
C Tsioufis ◽  
K Dimitriadis ◽  
N Vogiatzakis ◽  
A Kasiakogias ◽  
...  

Abstract Background/Introduction The clinical importance of a hypertensive response to exercise (HRE) in subjects with high normal blood pressure (BP) is not fully elucidated, while sympathetic overactivity and arterial stiffening are linked with adverse cardiovascular prognosis. Purpose The aim of this study was to assess the relation of HRE with sympathetic drive as assessed by muscle sympathetic nerve activity (MSNA) and arterial stiffness in subjects with high normal BP. Methods 42 subjects with high normal office BP [defined as office systolic BP=130–139 mmHg and office diastolic BP=85–89 mmHg (age: 53±9 years, 29 males, office BP: 134/84 mmHg, 24-hour BP: 114/72 mmHg)] with a negative treadmill exercise test (Bruce protocol) were divided into those with HRE (n=12) (peak exercise systolic BP ≥210mmHg in men and ≥190 mmHg in women) and those without HRE (n=30). Arterial stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (PWV) values. In all participants sympathetic drive was assessed by MSNA estimations based on established methodology (microneurography). Results Subjects with a HRE compared to those without exhibited higher waist circumference (108.2±5.3 vs 94.7±9.2 cm, p=0.001) and were characterized by greater levels of carotid to femoral PWV (8.5±0.8 vs 7.0±0.9 m/sec, p<0.001) and sympathetic nerve traffic as reflected by MSNA levels (41.1±1.5 vs 32.1±1.9 bursts per 100 heart beats, p<0.001), while did not differ regarding metabolic profile and left ventricular mass index (p=NS). In the total population, peak exercise systolic BP was related to 24-h systolic BP (r=0.229, p<0.05), PWV (r=0.218, p=0.002), and MSNA (r=0.214, p<0.05). Moreover, MSNA was related to waist circumference (r=0.33, p=0.004) and office systolic BP levels (r=0.31, p<0.05) but there was no association with PWV values (p=NS). Conclusion In subjects with high normal BP, a HRE identifies a state of arterial stiffening and sympathetic overdrive, as reflected by increased PWV and MSNA levels respectively. These finding suggest that exercise testing provides additional clinical information regarding the vascular status and modulation of sympathetic tone in this setting.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Landler ◽  
S Bro ◽  
B Feldt-Rasmussen ◽  
D Hansen ◽  
A.L Kamper ◽  
...  

Abstract Background The cardiovascular mortality of patients with chronic kidney disease (CKD) is 2–10 times higher than in the average population. Purpose To estimate the prevalence of abnormal cardiac function or structure across the stages CKD 1 to 5nonD. Method Prospective cohort study. Patients with CKD stage 1 to 5 not on dialysis, aged 30 to 75 (n=875) and age-/sex-matched controls (n=173) were enrolled consecutively. All participants underwent a health questionnaire, ECG, morphometric and blood pressure measurements. Blood and urine were analyzed. Echocardiography was performed. Left ventricle (LV) hypertrophy, dilatation, diastolic and systolic dysfunction were defined according to current ESC guidelines. Results 63% of participants were men. Mean age was 58 years (SD 12.6 years). Mean eGFR was 46.7 mL/min/1,73 m (SD 25.8) for patients and 82.3 mL/min/1,73 m (SD 13.4) for controls. The prevalence of elevated blood pressure at physical exam was 89% in patients vs. 53% in controls. Patients were more often smokers and obese. Left ventricular mass index (LVMI) was slightly, albeit insignificantly elevated at CKD stages 1 & 2 vs. in kontrols: 3.1 g/m2, CI: −0.4 to 6.75, p-value 0.08. There was no significant difference in LV-dilatation between patients and controls. Decreasing diastolic and systolic function was observed at CKD stage 3a and later: LVEF decreased 0.95% (CI: −1.5 to −0.2), GLS increased 0.5 (CI: 0.3 to 0.8), and OR for diastolic dysfunction increased 3.2 (CI 1.4 to 7.3) pr. increment CKD stage group. Conclusion In accordance to previous studies, we observe in the CPHCKD cohort study signs of early increase of LVMI in patients with CKD stage 1 & 2. Significant decline in systolic and diastolic cardiac function is apparent already at stage 3 CKD. Figure 1. Estimated GFR vs. GLS & histogram of GLS Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): The Capital Region of Denmark


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Tzortzis ◽  
I Ikonomidis ◽  
H Triantafyllidi ◽  
J Thymis ◽  
A Frogoudaki ◽  
...  

Abstract Background We investigated the effects of antihypertensive treatment on vascular function, longitudinal and torsional deformation in hypertensives. Methods In 200 untreated patients with arterial hypertension (age 52.5±11.6 years, 56% females), we measured at baseline and after a 3-year of antihypertensive treatment (160 received ACEi± diuretics and 40 CCBs± diuretics): a) 24h ambulatory blood pressure b) Carotid-femoral pulse wave velocity (PWV) b) Coronary flow reserve (CFR), LV mass index (LVMI), the global longitudinal strain (GLS) and diastolic (LongSRSE) strain rate, peak twisting (Tw-deg) and untwisting at mitral valve opening (UtwMVO), at peak E (UtwE) and at the end of the E wave (UtwendE) of the mitral inflow as well as twisting (TwVel-deg/sec) velocity using speckle tracking imaging. We calculated the % change of LV untwisting as difference between peakTw and UtwMVO, UtwpeakE and UtwendE. Results Compared to baseline, there was an improvement of GLS (−19.9±3.4 vs. −18.7±3.1%), LongSRS (−1.08±0.22 vs. −0.98±0.26 1/s), LongSRE (1.09±0.36 vs. 0.99±0.31 1/s), peak Tw (16.2±5.1 vs. 18.7±5.9 deg), Tw velocity, and the %LV untwisting (31.04±19.28 vs 26.02±15.69% at MVO, 60.04±19.78 vs 53.96±19.76% at peakE and 79.98±14.24 vs 75.90±17.01% at endE) post-treatment. In parallel, CFR (2.72±0.61 vs. 2.55±0.64), PWV (10.34±1.93 vs. 11.2±2.08 m/s) and LVMI were improved (p&lt;0.01 for all comparisons). By ANOVA, the interaction term between changes of all the above parameters and antihypertensive treatment (ACE inhibitors vs calcium channel blockers) was not significant (p&gt;0.05). By multivariate analysis, the reduction of 24h meanBP and PWV independently determined the respective improvement of GLS (b=0.478 and b=0.248 respectively), LongS (b=0.428 and b=0.201 respectively) as well as Twisting (b=0.449 and b=0.294 respectively) after adjusting for changes in LV mass, CFR and atherosclerotic risk factors (p&lt;0.05). Conclusions Long-term optimal blood pressure control with ACE inhibitors and CCBs improves LV longitudinal and torsional mechanics in hypertensives in parallel with arterial stiffness and blood pressure. This improvement in LV deformation and twisting was independently related to changes in arterial blood pressure and arterial stiffness. Funding Acknowledgement Type of funding source: None


2019 ◽  
Vol 127 (3) ◽  
pp. 753-759 ◽  
Author(s):  
Katharine D. Currie ◽  
Zion Sasson ◽  
Jack M. Goodman

This study sought to examine whether cardiovascular performance during exercise, assessed using the vascular-ventricular coupling index (VVC), was affected by exaggerated blood pressure (EBP) responses in endurance-trained athletes. Subjects were middle-aged endurance-trained men and women. Blood pressure measurements and left ventricular echocardiography were performed in a semiupright position at rest and during steady-state cycling at workloads that elicited 100–110 beats/min ( stage 1) and 130–140 beats/min ( stage 2). These data were used to calculate effective arterial elastance index ( EaI), left ventricular end-systolic elastance index ( ELVI), and their ratio (VVC). Additional measurements of left ventricular volumes and function (i.e., stroke volume, cardiac output, and longitudinal strain) and indirect assessments of peripheral vascular function (i.e., total arterial compliance and peripheral vascular resistance) were examined. Fourteen subjects with EBP (EBP+, 50% men) and 14 sex-matched subjects without EBP (EBP−) participated, with results presented as EBP+ versus EBP−. EaI and ELVI increased from rest to exercise while VVC decreased, but only ELVI was different between groups at stage 1 [7.6 (1.8) vs. 6.4 (1.0) mmHg·ml−1·m−2, P = 0.045] and stage 2 [10.3 (1.6) vs. 8.0 (1.7) mmHg·ml−1·m−2, P < 0.001]. Additional comparisons revealed no group difference in the contribution of the Frank-Starling mechanism or left ventricular and peripheral vascular function during exercise. The cardiovascular adjustment to exercise in athletes with EBP is achieved through a matched increase in both EaI and ELVI, and the absence of between-group differences in left ventricular or peripheral vascular function suggests that other factors may contribute to the EBP response. NEW & NOTEWORTHY Cardiovascular performance during submaximal exercise, assessed using vascular-ventricular coupling, is unaffected by exaggerated blood pressure (EBP) responses in endurance-trained athletes. The underlying mechanisms of EBP in athletes remain unknown as changes in left ventricular and peripheral vascular function during exercise were similar in athletes with and without EBP.


Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Robin C Shoemaker ◽  
Yu Wang ◽  
Sean Thatcher ◽  
Lisa Cassis

Angiotensin-1-7 (Ang-(1-7)) counteracts angiotensin II through effects at Mas receptors (MasR). We demonstrated that sexual dimorphism of obesity-hypertension was associated with dysregulated production of Ang-(1-7). However, the role of MasR in sexual dimorphism of obesity-hypertension has not been examined. MasR deficient mice have also been reported to exhibit deficits in cardiac function. In this study, we hypothesized that deficiency of the MasR would differentially regulate obesity-hypertension in male versus ( vs ) female mice. In addition, we quantified effects of MasR deficiency on cardiac function in obese male mice. Male and female MasR +/+ and -/- mice were fed a low fat (LF, 10%kcal) or high fat (HF, 60% kcal) diet for 16 weeks, and blood pressure was quantified by radiotelemetry. As demonstrated previously, male MasR +/+ mice (24 hr diastolic blood pressure, DBP: LF, 90 ± 3; HF, 96 ± 2 mmHg; P<0.05), but not females (LF, 85 ± 1; HF, 85 ± 2 mmHg), developed hypertension in response to HF feeding. MasR deficiency converted female HF-fed mice to an obesity-hypertension phenotype (DBP: 92 ± 1 mmHg; P<0.05). Surprisingly, male HF-fed MasR -/- mice exhibited reduced DBP compared to HF-fed MasR +/+ males (90 ± 1 vs 96 ± 2 mmHg; P<0.05). To define mechanisms for reductions in DBP of HF-fed male MasR -/- mice, we performed cardiac magnetic resonance (CMR) imaging in both genotypes at 1 month of HF feeding. MasR -/- mice had significantly reduced ejection fraction (EF) compared to MasR +/+ mice at baseline (51.4 ± 2.5 vs 59.3 ± 2.1%; P<0.05) and after one month of HF-feeding (49.8 ± 2.4 vs 52.6 ± 1.9%; P<0.05). Further, CMR imaging demonstrated a thickening of the ventricle wall in MasR -/- mice with 1 month of HF-feeding. MasR +/+ , but not MasR -/- mice, exhibited diet-induced reductions in EF (by 16%; P<0.05) at 1 month of HF feeding, which were reversed by infusion of Ang-(1-7). These results demonstrate that MasR contributes to sexual dimorphism of obesity-hypertension. Ang-(1-7) protects females from obesity-hypertension through the MasR. In contrast, reductions in DBP in obese male mice with MasR deficiency may arise from deficits in cardiac function. These results suggest that MasR agonists may be effective therapies for obesity-associated cardiovascular conditions.


Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Joseph T Flynn ◽  
Philip Khoury ◽  
Joshua A Samuels ◽  
Marc B Lande ◽  
Kevin Meyers ◽  
...  

We investigated whether blood pressure (BP) phenotype based on clinic & 24-hour ambulatory BP (ABP) was associated with intermediate markers of cardiovascular disease (CVD) in 374 adolescents enrolled in a study of the relationship of BP to CV risk. Clinic BP was measured by auscultation and categorized using the 2017 AAP guideline. ABP was measured for 24 hours by an oscillometric device and analyzed using the adult ABP wake SBP cut-point (130 mmHg). This created 4 BP phenotype groups: normal BP (n=224), white coat hypertensive (n=48), ambulatory hypertensive (n=57) & masked hypertensive (n=45). Echocardiographic parameters & carotid-femoral pulse wave velocity (PWVcf) were measured to assess CVD risk. Left ventricular mass (LVM) was lowest in the normal BP group, whereas multiple measures of cardiac function and PWVcf were worse in the masked and ambulatory hypertensive groups: Generalized linear models adjusted for body mass index (BMI) were constructed to examine the associations between BP phenotype and the measured CVD variables. ABP phenotype was an independent predictor of LVM, diastolic and systolic function and PWVcf in the unadjusted model. ABP phenotype remained significantly associated with diastolic function (E/e’, e’/a’), systolic function (ejection fraction) and increased arterial stiffness (PWVcf) after adjustment for BMI percentile (all p<=0.05). We conclude that BP phenotype is an independent predictor of markers of increased CVD risk in adolescents, including impaired cardiac function and increased vascular stiffness. ABP monitoring has an important role in CVD risk assessment in youth.


2006 ◽  
Vol 111 (6) ◽  
pp. 365-372 ◽  
Author(s):  
Wolfgang Lieb ◽  
Juliane Bolbrinker ◽  
Angela Döring ◽  
Hans-Werner Hense ◽  
Jeanette Erdmann ◽  
...  

A polymorphism in the cytochrome P450 3A CYP3A5 enzyme has been implicated in BP (blood pressure) control and arterial hypertension. Carriers of the CYP3A5*1 allele had high, whereas homozygous carriers of the CYP3A5*3 allele exhibit low, CYP3A5 expression in the kidney, where CYP3A5 represents the major CYP3A enzyme. The aim of the present study was to investigate the association of the CYP3A5*1 allele with BP, arterial hypertension, LVM [(left ventricular) mass] and LV geometry in a large Caucasian-population-based cohort. We compared BP, LVM and the prevalence of hypertension between carriers (CYP3A5*1/*1 and CYP3A5*1/*3 genotypes) and non-carriers (CYP3A5*3/*3 genotype) of the CYP3A5*1 allele in the echocardiographic substudy of the third MONICA (MONItoring trends and determinants in CArdiovascular disease) Augsburg survey. After exclusion of 269 individuals who were taking antihypertensive medication, 530 women and 554 men were available for analysis, revealing allele frequencies of 5.8 and 94.2% for the CYP3A5*1 and CYP3A5*3 alleles respectively. Overall, the presence of the CYP3A5*1 allele exhibited no effect on systolic or diastolic BP in either gender. One-third of the individuals in this cohort were hypertensive (BP ≥140/90 mmHg), and the genotype distribution between normotensive and hypertensive individuals revealed no association between CYP3A5*1 and hypertension after adjustment for age, BMI and gender (odds ratio, 1.02; P=0.92). Moreover, no effect of CYP3A5*1 on LVM, thickness of the septal and posterior wall and LV end-diastolic diameter was found. We conclude that CYP3A5*1 exhibits no significant effect on BP, LVM and LV geometry in the KORA/MONICA echocardiographic substudy.


2021 ◽  
Vol 89 (1) ◽  
pp. 20-26
Author(s):  
Sebastián Galdeano ◽  
Damián Holownia ◽  
Darío Palavecino ◽  
José Daniel Abregú ◽  
María Silvina Rivas Jordan ◽  
...  

Background: The Quilmes community includes 2,400 inhabitants of the middle and high mountains of Tucumán (1,800 to 4,000 meters above sea level). The purpose of the present study was to know their cardiovascular health status. Methods: A cross-sectional descriptive quantitative investigation was carried out in people belonging to the Quilmes community who voluntarily attended the planned evaluation on September 27-29, 2018. Results: Two hundred and two settlers were studied (125 women and 77 men; 48±1.4 years), 23% of them had hypertension (HTN); 14% were smokers; 4.9% had diabetes; 18% had dyslipidemia (DLP) and 25% usually consumed alcohol (1.0 ± 0.4 L/day). Also, 29% were overweight and 36% obese. High blood pressure (BP) was recorded in 48 individuals at the time of the study. Blood pressure decreased in the third compared to the first measurement, whereas heart rate increased in the third assessment (74±1 beats per minute vs. 77±1; p <0.01). Oxygen saturation (95.0±0.2%) was negatively correlated with age (Pearson r: -0.266; p <0.001). In individuals with normal BP, ultrasound E/ratio was higher (1.2±0.0) and left ventricular posterior wall thickness was lower (8.5±0.5 mm) than in those with elevated BP (0.92±0.1 and 9.0±0.3, respectively, p <0.001). Twenty-four percent of individuals had atherosclerotic plaques and 120 had DLP. Conclusions: The Quilmes population presents a prevalence of cardiovascular risk factors similar to that of urban centers, which could lead to an increase in cardiovascular morbidity and mortality in the coming years


2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Vineeta Tanwar ◽  
Kristin I Stanford ◽  
Loren E Wold

Objective: Exposure to particulate matter 2.5 μm (PM2.5) during intrauterine development is associated with adverse cardiovascular outcomes at adulthood. Deteriorations in cardiac function are observed with increased myocardial demand in PM2.5-exposed individuals. The goal of this study was to determine the effects of in utero PM2.5exposure on exercise training capacity and cardiac function in adult mice. Methods: Female FVB mice were exposed either to filtered air (FA) or PM2.5at an average concentration of 73.61μg/m 3 for 6h/day, 7days/wk throughout pregnancy. 12wk old male offspring from exposed dams were assigned to in utero FA (n=5) or PM2.5 (n=5) exposed groups which underwent exercise training for 3 weeks (housed with running wheels for 3 weeks). We measured total distance travelled and performed echocardiography at baseline, 1, 2 and 3 weeks. Results: There was a progressive decrease in total distance travelled each week in the in utero PM2.5 exposed mice (Week 1: 12.2±3.46 Km FA, 5.32±2.06 Km PM2.5; Week 2: 41.4±9.62 Km FA, 17.28±6.60 Km PM2.5; Week 3: 61.8±16.59 Km FA, 25.92.±8.62 Km PM2.5) compared to the in utero FA exposed mice. When comparing to their respective sedentary counterparts, the FA exercise group showed increased fractional shortening (%FS), left ventricular end systolic (LVESd) and diastolic (LVEDd) diameters, suggesting eccentric hypertrophy. There was a modest decrease in %FS and marked increase in posterior wall thickness during diastole (PWTd) in the PM2.5 exercise group suggesting concentric hypertrophy. Comparison of in utero FA vs PM2.5 exercise groups after 3 weeks of exercise training showed reduced %FS and marked decrease in LVEDd in the PM2.5 exercise group compared to the FA exercise group. Furthermore, a decrease in PWTs and increased PWTd was also observed in the PM2.5 group compared to FA controls. Conclusions: In utero PM2.5exposure reduced exercise capacity at adulthood and the development of both systolic and diastolic dysfunction. Thus, our study showed that individuals residing in high pollution areas are predisposed to develop cardiac dysfunction under conditions of increased myocardial demand.


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