Objective

Abdominal aortic aneurysm (AAA) is commonly defined as localised aortic dilatation with a diameter > 30 mm. The pathophysiology of AAA includes chronic inflammation and enzymatic degradation of elastin, possibly increasing aortic wall stiffness and pulse wave velocity (PWV). Whether aortic stiffness is more prominent in the abdominal aorta at the aneurysm site is not elucidated. The aim of this study was to evaluate global and regional aortic PWV in patients with AAA.

Methods

Experimental study of local PWV in the thoracic descending and abdominal aorta in patients with AAA and matched controls. The study cohort comprised 25 patients with an AAA > 30 mm (range 36 – 70 mm, all male, age range 65 – 76 years) and 27 age and sex matched controls free of AAA. PWV was measured with applanation tonometry (carotid-femoral PWV, cfPWV) as well as a 4D flow MRI technique, assessing regional aortic PWV. Blood pressure and anthropometrics were measured.

Results

Global aortic PWV was greater in men with an AAA than controls, both by MRI (AAA 8.9 ± 2.4 m/s vs. controls 7.1 ± 1.5 m/s; p = .007) and cfPWV (AAA 11.0 ± 2.1 m/s vs. controls 9.3 ± 2.3 m/s; p = .007). Regionally, PWV was greater in the abdominal aorta in the AAA group (AAA 7.0 ± 1.8 m/s vs. controls 5.8 ± 1.0 m/s; p = .022), but similar in the thoracic descending aorta (AAA 8.7 ± 3.2 m/s vs. controls 8.2 ± 2.4 m/s; p = .59). Furthermore, PWV was positively associated with indices of central adiposity both in men with AAA and controls.

Conclusion

PWV is higher in men with AAA compared with matched controls in the abdominal but not the thoracic descending aorta. Furthermore, aortic stiffness was linked with central fat deposition. It remains to be seen whether there is a causal link between AAA and increased regional aortic stiffness.

Aims Understanding the mechanisms underlying ascending aortic dilation is imperative for refined risk stratification of these patients, particularly among incidentally identified patients, most commonly presenting with tricuspid valves. The aim of this study was to explore associations between ascending aortic haemodynamics, assessed using four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR), and circulating biomarkers in aortic dilation. Methods and results Forty-seven cases with aortic dilation (diameter >= 40 mm) and 50 sex-and age-matched controls (diameter < 40 mm), all with tricuspid aortic valves, underwent 4D flow CMR and venous blood sampling. Associations between flow displacement, wall shear stress (WSS), and oscillatory shear index in the ascending aorta derived from 4D flow CMR, and biomarkers including interleukin-6, collagen type I alpha 1 chain, metalloproteinases (MMPs), and inhibitors of MMPs derived from blood plasma, were investigated. Cases with dilation exhibited lower peak systolic WSS, higher flow displacement, and higher mean oscillatory shear index compared with controls without dilation. No significant differences in biomarkers were observed between the groups. Correlations between haemodynamics and biomarkers were observed, particularly between maximum time-averaged WSS and interleukin-6 (r = 0.539, P < 0.001), and maximum oscillatory shear index and collagen type I alpha 1 chain (r = -0.575, P < 0.001 in cases). Conclusion Significant associations were discovered between 4D flow CMR derived whole-cardiac cycle WSS and circulating biomarkers representing inflammation and collagen synthesis, suggesting an intricate interplay between haemodynamics and the processes of inflammation and collagen synthesis in patients with early aortic dilation and tricuspid aortic valves.

Objective: Abdominal aortic aneurysm (AAA) is associated with dilatation of central elastic arteries, while it is uncertain whether peripheral muscular arteries are affected. The aim of this study was to investigate radial artery diastolic lumen diameter (LD), wall thickness, and circumferential wall stress (CWS) in patients with AAA. Methods: We included 130 men with AAA (mean age, 70.4 ± 3.5 years) and 61 men without AAA (mean age, 70.5 ± 3.2 years) in the study. High-frequency ultrasound examination (50 MHz) was used to measure radial artery diameter, wall thickness, and CWS was calculated. Results: Men with AAA exhibited smaller radial artery LD (2.34 ± 0.42 mm vs 2.50 ± 0.38 mm; P <.01), thicker intima (0.094 ± 0.024 mm vs 0.081 ± 0.018 mm; P <.001), similar intima-media (0.28 ± 0.05 vs 0.26 ± 0.05 mm; P = NS), and lower CWS (42.9 ± 10.2 kPa vs 48.6 ± 11.4 kPa; P <.001), compared with controls. Subgroup analyses including all patients showed smaller LD and thicker intima in patients on statin therapy versus no statin therapy and current/ex-smoking versus never smoking. Individuals with hypertension versus no hypertension also presented with thicker intima, but with no difference in LD. Conclusions: AAAs demonstrated a smaller LD and thicker intima in the radial artery, in contrast with the theory of a general dilating diathesis of the arteries. Apart from AAA, other factors such as atherosclerosis, smoking habits, and hypertension might also be determinants of radial artery caliber and thickness. Clinical Relevance: The clinical relevance of this study is the added insight into the pathophysiology of abdominal aortic aneurysm (AAA). Today, the management of AAA is focused on reduction of general cardiovascular risk factors and treatment is based on surgical approaches when the AAA is already manifest. By shedding light on unknown pathophysiological aspects of AAA, it will eventually be possible to develop targeted pharmacological treatments to prevent the formation of AAA, to halt disease progression, and to find early cardiovascular markers of AAA. © 2022 Society for Vascular Surgery

Although vasovagal syncope (VVS) is a common clinical condition, the underlying pathophysiology is not fully understood. A decrease in cardiac output has recently been suggested as a factor in orthostatic VVS. The aim was to investigate compensatory mechanisms to maintain central blood volume and venous return during hypovolemic stress in women with VVS. Fourteen VVS women (25.7 +/- 5.0 yr) and 15 matched controls (22.8 +/- 3.2 yr) were investigated. Single-step and graded lower body negative pressure (LBNP) to presyncope were used to create hypovolemic stress. Peripheral mobilization of venous blood from the arm (capacitance response and net capillary fluid absorption) and lower limb blood pooling (calf capacitance response) were evaluated using a volumetric technique. Cardiovascular responses and plasma norepinephrine (P-NE) were measured. Resting P-NE was elevated in VVS women (P amp;lt; 0.01). Despite a similar hypovolemic stimulus, the increase in P-NE was blunted (P amp;lt; 0.01) and the maximal percent increase in total peripheral resistance was reduced (P amp;lt; 0.05) during graded LBNP in VVS women. The arm capacitance response was slower (P amp;lt; 0.05) and reduced in VVS women at higher levels of LBNP (P amp;lt; 0.05). Capillary fluid absorption from extra-to intravascular space was reduced by similar to 40% in VVS women (P amp;lt; 0.05). Accordingly, the reduction in cardiac output was more pronounced (P amp;lt; 0.05). In conclusion, in VVS women, mobilization of peripheral venous blood and net fluid absorption from tissue to blood during hypovolemic stress were decreased partly as a result of an attenuated vasoconstrictor response. This may seriously impede maintenance of cardiac output during hypovolemic stress and could contribute to the pathogenesis of VVS.

The influence of lower limb venous compliance on orthostatic vasovagal syncope (VVS) is uncertain. The most widespread technique to calculate venous compliance uses a nonphysiological quadratic regression equation. Our aim was therefore to construct a physiologically derived venous wall model (VWM) for calculation of calf venous compliance and to determine the effect of venous compliance on tolerance to maximal lower body negative pressure (LBNP). Venous occlusion plethysmography was used to study calf volume changes in 15 women with VVS (25.5 +/- 1.3 yr of age) and 15 controls (22.8 +/- 0.8 yr of age). The fit of the VWM and the regression equation to the experimentally induced pressure-volume curve was examined. Venous compliance was calculated as the derivative of the modeled pressure-volume relationship. Graded LBNP to presyncope was used to determine the LBNP tolerance index (LTI). The VWM displayed a better fit to the experimentally induced pressure-volume curve (P < 0.0001). Calf blood pooling was similar in the groups and was not correlated to the LTI (r = 0.204, P = 0.30). Venous compliance was significantly reduced at low venous pressures in women with VVS (P = 0.042) and correlated to the LTI (r = 0.459, P = 0.014) in the low pressure range. No correlation was found between venous compliance at high venous pressures and the LTI. In conclusion, the new VWM accurately adopted the curvilinear pressure-volume curve, providing a valid characterization of venous compliance. Reduced venous compliance at low venous pressures may adversely affect mobilization of peripheral venous blood to the central circulation during hypovolemic circulatory stress in women with VVS.

Background and Aim: Slower lower limb blood pooling and associated blunted sympathetic activation has been detected in healthy women prone to orthostatic syncope. Whether these findings are true also for patients with vasovagal syncope (WS) is unknown. The aim was to investigate initial blood pooling time (pooling(time), time to 50% of total blood pooling) together with hemodynamic responses and orthostatic tolerance during lower body negative pressure (LBNP) in WS and healthy controls. Methods and Results: Fourteen WS women (25.7 +/- 1.3 years) and 15 healthy women (22.8 +/- 0.8 years) were subjected to single-step and graded LBNP to pre-syncope. Lower limb blood pooling (ml 100 ml(-1)), poolingtime (s), hemodynamic responses and LBNP-tolerance were evaluated. LBNP induced comparable lower limb blood pooling in both groups (controls, 3.1 +/- 0.3; WS, 2.9 +/- 0.3 ml 100 ml(-1), P = 0.70). In controls, shorter pooling(time) correlated to higher LBNP-tolerance (r = -0.550, P amp;lt; 0.05) as well as better maintained stroke volume (r =-0.698, P amp;lt; 0.01) and cardiac output (r = -0.563, P amp;lt; 0.05). In contrast, shorter poolingtime correlated to lower LBNP-tolerance in VVS (r = 0.821, P amp;lt; 0.001) and larger decline in stroke volume (r = 0.611, P 0.05). Furthermore, in controls, shorter poolingtime correlated to baroreflex-mediated hemodynamic changes during LBNP, e.g., increased vasoconstriction (P amp;lt; 0.001). In VVS, poolingtime was not correlated with LBNP-induced baroreceptor unloading, but rather highly correlated to resting calf blood flow (P amp;lt; 0.001). Conclusions: Shorter poolingtime seems to elicit greater sympathetic activation with a concomitant higher orthostatic tolerance in healthy women. The contrasting findings in AS indicate a deteriorated vascular sympathetic control suggesting well-defined differences already in the initial responses during orthostatic stress.

PURPOSE: Calf venous compliance (C calf) is commonly evaluated with venous occlusion plethysmography (VOP) during a standard cuff deflation protocol. However, the technique relies on two not previously validated assumptions concerning thigh cuff pressure (P cuff) transmission and the impact of net fluid filtration (F filt) on C calf. The aim was to validate VOP in the lower limb and to develop a model to correct for F filt during VOP.

METHODS: Strain-gauge technique was used to study calf volume changes in 15 women and 10 age-matched men. A thigh cuff was inflated to 60 mmHg for 4 and 8 min with a subsequent decrease of 1 mmHg s(-1). Intravenous pressure (P iv) was measured simultaneously. C calf was determined with the commonly used equation [Compliance = β 1 + 2β 2 × P cuff] describing the pressure-compliance relationship. A model was developed to identify and correct for F filt.

RESULTS: Transmission of P cuff to P iv was 100 %. The decrease in P cuff correlated well with P iv reduction (r = 0.99, P < 0.001). Overall, our model showed that C calf was underestimated when F filt was not accounted for (all P < 0.01). F filt was higher in women (P < 0.01) and showed a more pronounced effect on C calf compared to men (P < 0.05). The impact of F filt was similar during 4- and 8-min VOP.

CONCLUSIONS: P cuff is an adequate substitute for P iv in the lower limb. F filt is associated with an underestimation of C calf and differences in the effect of F filt during VOP can be accounted for with the correction model. Thus, our model seems to be a valuable tool in future studies of venous wall function.

NEW FINDINGS: What is the central question of this study? Orthostatic stress is mostly caused by venous blood pooling in the lower limbs. Venous distension elicits sympathetic responses, and increased distension speed enhances the cardiovascular response. We examine whether lower limb blood pooling rate during lower body negative pressure is linked to orthostatic intolerance. What is the main finding and its importance? A similar amount of blood was pooled in the lower limb, but at a slower rate in women who developed signs of orthostatic intolerance. The difference in blood pooling rate increased with orthostatic stress and was most prominent at a presyncope-inducing level of lower body negative pressure. The findings have implications for the pathophysiology as well as treatment of orthostatic intolerance. Vasovagal syncope is common in young women, but its aetiology remains elusive. Orthostatic stress-induced lower limb blood pooling is linked with central hypovolaemia and baroreceptor unloading. Venous distension in the arm elicits a sympathetic response, which is enhanced with more rapid distension. Our aim was to study both the amount and the speed of lower limb pooling during orthostatic stress and its effects on compensatory mechanisms to maintain cardiovascular homeostasis in women with orthostatic intolerance. Twenty-seven healthy women, aged 20-27 years, were subjected to a lower body negative pressure (LBNP) of 11-44 mmHg. Five women developed symptoms of vasovagal syncope (orthostatic intolerant) and were compared with the remaining women, who tolerated LBNP well (orthostatic tolerant). Lower limb blood pooling, blood flow and compensatory mobilization of venous capacitance blood were measured. Lower body negative pressure induced equal lower limb blood pooling in both groups, but at a slower rate in orthostatic intolerant women (e.g. time to 50% of total blood pooling, orthostatic intolerant 44 ± 7 s and orthostatic tolerant 26 ± 2 s; P < 0.001). At presyncope-inducing LBNP, the mobilization of venous capacitance blood was both reduced (P < 0.05) and much slower in orthostatic intolerant women (P = 0.0007). Orthostatic intolerant women elicited blunted arterial vasoconstriction at low-grade LBNP, activating only cardiopulmonary baroreceptors, while orthostatic tolerant women responded with apparent vasoconstriction (P < 0.0001). In conclusion, slower lower limb blood pooling could contribute to orthostatic intolerance in women. Mobilization of venous capacitance blood from the peripheral to the central circulation was both slower and decreased; furthermore, reduced cardiopulmonary baroreceptor sensitivity was found in women who developed orthostatic intolerance. Further studies including women who experience syncope in daily life are needed.

BACKGROUND: For the large population of elderly patients with cardiovascular disease, it is crucial to identify clinically relevant measures of biological age and their contribution to risk. Frailty is denoting decreased physiological reserves and increased vulnerability. We analysed the manner in which the variable frailty is associated with 1-year outcomes for elderly non-ST-segment elevation myocardial infarction (NSTEMI) patients. METHODS AND RESULTS: Patients aged 75 years or older, with diagnosed NSTEMI were included at three centres, and clinical data including judgment of frailty were collected prospectively. Frailty was defined according to the Canadian Study of Health and Aging Clinical Frailty Scale. Of 307 patients, 149 (48.5%) were considered frail. By Cox regression analyses, frailty was found to be independently associated with 1-year mortality after adjusting for cardiovascular risk and comorbid conditions (hazard ratio 4.3, 95% CI 2.4-7.8). The time to the first event was significantly shorter for frail patients than for nonfrail (34 days, 95% CI 10-58, p = 0.005). CONCLUSIONS: Frailty is strongly and independently associated with 1-year mortality. The combined use of frailty and comorbidity may constitute an important risk prediction concept in regard to cardiovascular patients with complex needs.