Aortic haemodynamics: the effects of habitual endurance exercise, age and muscle sympathetic vasomotor outflow in healthy men

Purpose We determined the effect of habitual endurance exercise and age on aortic pulse wave velocity (aPWV), augmentation pressure (AP) and systolic blood pressure (aSBP), with statistical adjustments of aPWV and AP for heart rate and aortic mean arterial pressure, when appropriate. Furthermore, we assessed whether muscle sympathetic nerve activity (MSNA) correlates with AP in young and middle-aged men. Methods Aortic PWV, AP, aortic blood pressure (applanation tonometry; SphygmoCor) and MSNA (peroneal microneurography) were recorded in 46 normotensive men who were either young or middle-aged and endurance-trained runners or recreationally active nonrunners (10 nonrunners and 13 runners within each age-group). Between-group differences and relationships between variables were assessed via ANOVA/ANCOVA and Pearson product-moment correlation coefficients, respectively. Results Adjusted aPWV and adjusted AP were similar between runners and nonrunners in both age groups (all, P > 0.05), but higher with age (all, P < 0.001), with a greater effect size for the age-related difference in AP in runners (Hedges’ g, 3.6 vs 2.6). aSBP was lower in young (P = 0.009; g = 2.6), but not middle-aged (P = 0.341; g = 1.1), runners compared to nonrunners. MSNA burst frequency did not correlate with AP in either age group (young: r = 0.00, P = 0.994; middle-aged: r = − 0.11, P = 0.604). Conclusion There is an age-dependent effect of habitual exercise on aortic haemodynamics, with lower aSBP in young runners compared to nonrunners only. Statistical adjustment of aPWV and AP markedly influenced the outcomes of this study, highlighting the importance of performing these analyses. Further, peripheral sympathetic vasomotor outflow and AP were not correlated in young or middle-aged normotensive men.

Cystamine reduces vascular stiffness in Western diet-fed female mice

Consumption of diets high in fat, sugar and salt (Western diet, WD) is associated with accelerated arterial stiffening, a major independent risk factor for cardiovascular disease (CVD). Obese women are more prone to develop arterial stiffening leading to more frequent and severe CVD compared to men. As tissue transglutaminase (TG2) has been implicated in vascular stiffening, our goal herein was to determine the efficacy of cystamine, a non-specific TG2 inhibitor, at reducing vascular stiffness in female mice chronically fed a WD. Three experimental groups of female mice were created. One was fed regular chow diet (CD) for 43 weeks starting at four weeks of age. The second was fed a WD for the same 43 weeks, whereas a third cohort was fed WD, but also received cystamine (216 mg/kg/d) in the drinking water during the last eight weeks on the diet (WD+C). All vascular stiffness parameters assessed, including aortic pulse wave velocity and the incremental modulus of elasticity of isolated femoral and mesenteric arteries, were significantly increased in WD- vs. CD-fed mice, and reduced in WD+C vs. WD-fed mice. These changes coincided with respectively augmented and diminished vascular wall collagen and F-actin content, with no associated effect in blood pressure. In cultured human vascular smooth muscle cells, cystamine reduced TG2 activity, F-actin/G-actin ratio, collagen compaction capacity and cellular stiffness. We conclude that cystamine treatment represents an effective approach to reduce vascular stiffness in female mice in the setting of WD consumption, likely due to its TG2 inhibitory capacity.

The Novel Bone Alkaline Phosphatase Isoform B1x Is Associated with Improved 5-Year Survival in Chronic Kidney Disease

Circulating alkaline phosphatase (ALP) is an independent cardiovascular risk marker. Serum bone ALP (BALP) isoforms indicate bone turnover and comprise approximately 50% of total circulating ALP. In chronic kidney disease (CKD), mortality is highest in patients with increased ALP and BALP and low bone turnover. However, not all low bone turnover states are associated with increased mortality. Chronic inflammation and oxidative stress, features of protein energy wasting syndrome, induce cardiovascular BALP activity and fibro-calcification, while bone turnover is suppressed. Circulating BALP isoform B1x is associated with low ALP and low bone turnover and has been exclusively detected in CKD. We investigated the association of serum B1x with survival, abdominal aortic calcification (AAC) score, and aortic pulse wave velocity (PWV) in CKD. Serum ALP, BALP isoforms, parathyroid hormone (PTH), PWV, and AAC were measured repeatedly over 2 years in 68 prevalent dialysis patients. Mortality was assessed after 5 years. B1x was detected in 53 patients. A competing risk analysis revealed an association of B1x with improved 5-year survival; whereas, baseline PWV, but not AAC score, predicted mortality. However, PWV improved in 26 patients (53%), and B1x was associated with variation of PWV over time (p = 0.03). Patients with B1x had lower PTH and total ALP, suggesting an association with lower bone turnover. In conclusion, B1x is associated with time-varying PWV, lower circulating ALP, and improved survival in CKD, and thus may be an indicator of a reduced cardiovascular risk profile among patients with low bone turnover.

Elevated Aortic Pulse Wave Velocity Relates to Longitudinal Gray and White Matter Changes

Objective: To determine whether baseline aortic stiffness, measured by aortic pulse wave velocity (PWV), relates to longitudinal cerebral gray or white matter changes among older adults. Baseline cardiac magnetic resonance imaging will be used to assess aortic PWV while brain magnetic resonance imaging will be used to assess gray matter and white matter hyperintensity (WMH) volumes at baseline, 18 months, 3 years, 5 years, and 7 years. Approach and Results: Aortic PWV (m/s) was quantified from cardiac magnetic resonance. Multimodal 3T brain magnetic resonance imaging included T 1 -weighted imaging for quantifying gray matter volumes and T 2 -weighted fluid-attenuated inversion recovery imaging for quantifying WMHs. Mixed-effects regression models related baseline aortic PWV to longitudinal gray matter volumes (total, frontal, parietal, temporal, occipital, hippocampal, and inferior lateral ventricle) and WMH volumes (total, frontal, parietal, temporal, and occipital) adjusting for age, sex, race/ethnicity, education, cognitive diagnosis, Framingham stroke risk profile, APOE (apolipoprotein E)-ε4 carrier status, and intracranial volume. Two hundred seventy-eight participants (73±7 years, 58% male, 87% self-identified as non-Hispanic White, 159 with normal cognition, and 119 with mild cognitive impairment) from the Vanderbilt Memory & Aging Project (n=335) were followed on average for 4.9±1.6 years with PWV measurements occurring from September 2012 to November 2014 and longitudinal brain magnetic resonance imaging measurements occurring from September 2012 to June 2021. Higher baseline aortic PWV was related to greater decrease in hippocampal (β=−3.6 [mm 3 /y]/[m/s]; [95% CI, −7.2 to −0.02] P =0.049) and occipital lobe (β=−34.2 [mm 3 /y]/[m/s]; [95% CI, −67.8 to −0.55] P =0.046) gray matter volume over time. Higher baseline aortic PWV was related to greater increase in WMH volume over time in the temporal lobe (β=17.0 [mm 3 /y]/[m/s]; [95% CI, 7.2–26.9] P <0.001). All associations may be driven by outliers. Conclusions: In older adults, higher baseline aortic PWV related to greater decrease in gray matter volume and greater increase in WMHs over time. Because of unmet cerebral metabolic demands and microvascular remodeling, arterial stiffening may preferentially affect certain highly active brain regions like the temporal lobes. These same regions are affected early in the course of Alzheimer disease.

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

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. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Foundation Table 1 Table 2

Stress-induced cardiovascular responses to cold pressure test in healthy young subjects

Hypertension is one of the leading diseases of the cardiovascular system. It is manifested by changes in arterial stiffness. Cardiovascular reactivity, especially blood pressure (BP), changes during the cold pressor test (CPT) depending on various factors. Undoubtedly, stress is one of the most important factors. The aim of the study is to investigate the various effects of CPT on cardiovascular responses in healthy young subjects. 56 healthy individuals aged between 21 and 26 years have been investigated. The Cardiovascular responses (BP, heart rate, aortic pulse wave velocity) to CPT were recorded by using the applanation tonometry. The Medical Outcomes Study Sleep Scale and the State-Trait Anxiety Inventory were assessed. 32,14%(n=18) of individuals who had showed difference in systolic BP more than 22 mm of Hg and difference in diastolic BP more than 18 mm of Hg after the CPT were defined as hyperreactors. Hyperreactors showed a significantly higher increase in sleep disturbances (P > 0.01) and anxiety when compared to the normoreaktors. The CPT used to diagnose cardiovascular reactivity in young individuals and the assessment of perceived stress can help identify candidates for a future risk of hypertonic disease. Keywords: Cold pressor test; cardiovascular reactivity; applanation tonometry; blood pressure; stress

Sex moderations in the relationship between aortic stiffness, cognition, and cerebrovascular reactivity in healthy older adults

It is well established that sex differences exist in the manifestation of vascular diseases. Arterial stiffness (AS) has been associated with changes in cerebrovascular reactivity (CVR) and cognitive decline in aging. Specifically, older adults with increased AS show a decline on executive function (EF) tasks. Interestingly, the relationship between AS and CVR is more complex, where some studies show decreased CVR with increased AS, and others demonstrate preserved CVR despite higher AS. Here, we investigated the possible role of sex on these hemodynamic relationships. Acquisitions were completed in 48 older adults. Pseudo-continuous arterial spin labeling (pCASL) data were collected during a hypercapnia challenge. Aortic pulse wave velocity (PWV) data was acquired using cine phase contrast velocity series. Cognitive function was assessed with a comprehensive neuropsychological battery, and a composite score for EF was calculated using four cognitive tests from the neuropsychological battery. A moderation model test revealed that sex moderated the relationship between PWV and CVR and PWV and EF, but not between CVR and EF. Together, our results indicate that the relationships between central stiffness, cerebral hemodynamics and cognition are in part mediated by sex.

Association of Aortic Pulse Wave Velocity with the Severity of Coronary Artery Disease in Patients with Non-ST-Segment Elevation Myocardial Infarction

Background: Noninvasive assessment of arterial stiffness with aortic pulse wave velocity (PWV) may serve as a useful adjunct to the cardiovascular risk stratification and risk management. The aim of this study was to evaluate the association between aortic PWV and severity of coronary artery disease (CAD) in patients with non-STsegment elevation myocardial infarction (NSTEMI). Methods: This cross sectional analytical study was conducted over 100 NSTEMI patients who were purposively selected and agreed to do coronary angiogram during index hospital admission. PWV was assessed noninvasively using the SphygmoCor® system on the day before coronary angiogram (CAG). Study subjects were divided into two groups on the basis of PWV. In group I: PWV was ≤10 m/sec and in group II: PWV was > 10 m/sec. Fifty patients in each group. Angiographic severity of CAD was assessed by vessel score, Friesinger score and Leaman score. Results: Vessel score 2 and 3 were significantly (p<0.05) higher in group II and vessel score 0 and 1 were significantly (p<0.05) higher in group I. The mean PWV in the group with normal angiographic results was 8.21±1.8 m/sec, and in patients with single-vessel disease it was 9.88±2.02 m/sec. In those with double and triple vessel disease the mean PWV was found 11.95±2.61 m/sec and 14.37±2.96 m/sec respectively. There was a significant difference of the mean value of PWV among the vessel involvement group (p=0.001). Normal and low Friesinger score were significantly (p<0.05) higher in group I patients. Intermediate and high Friesinger score were significantly (p<0.05) higher in group II patients. Increased PWV was significantly associated with the presence and severity of CAD in NSTEMI. This association showed a positive linear relation between the values of PWV and vessel score (r=0.65, p=0.01), Friesinger score (r=0.61, p=0.01), and Leaman score (r=0.36, p=0.01). Conclusion: From this study it may be stated that arterial stiffness, as measured by the aortic PWV, is an independent predictor of the presence and extent of CAD. Measurements of aortic PWV in NSTEMI can detect high risk patients requiring an early invasive strategy over a delayed invasive strategy. Bangladesh Heart Journal 2021; 36(1) : 38-46