Pressure-dependence of arterial stiffness: potential clinical implications

Background: Arterial stiffness measures such as pulse wave velocity (PWV) have a known dependence on actual blood pressure, requiring consideration in cardiovascular risk assessment and management. Given the impact of ageing on arterial wall structure, the pressure-dependence of PWV may vary with age. Methods: Using a noninvasive model-based approach, combining carotid artery echo-tracking and tonometry waveforms, we obtained pressure-area curves in 23 hypertensive patients at baseline and after 3 months of antihypertensive treatment. We predicted the follow-up PWV decrease using modelled baseline curves and follow-up pressures. In addition, on the basis of these curves, we estimated PWV values for two age groups (mean ages 41 and 64 years) at predefined hypertensive (160/90 mmHg) and normotensive (120/80mmHg) pressure ranges. Results: Follow-up measurements showed a near 1 m/s decrease in carotid PWV when compared with baseline, which fully agreed with our model-prediction given the roughly 10mmHg decrease in diastolic pressure. The stiffness-blood pressure-age pattern was in close agreement with corresponding data from the 'Reference Values for Arterial Stiffness' study, linking the physical and empirical bases of our findings. Conclusion: Our study demonstrates that the innate pressure-dependence of arterial stiffness may have implications for the clinical use of arterial stiffness measurements, both in risk assessment and in treatment monitoring of individual patients. We propose a number of clinically feasible approaches to account for the blood pressure effect on PWV measurements

Quantitative assessment of cardiac load-responsiveness during extracorporeal life support: case and rationale

We describe a case of a patient assisted by extracorporeal life support, in which we obtained the dynamic filling index, a measure for venous volume during extracorporeal life support, and used this index to assess cardiac load-responsiveness during acute reloading. While reloading, the obtained findings on cardiac pump function by the dynamic filling index were supported by trans-esophageal echocardiography and standard pressure measurement. This suggests that the dynamic filling index can be used to assess cardiac load-responsiveness during extracorporeal life support

The Maastricht Acquisition Platform for Studying Mechanisms of Cell–Matrix Crosstalk (MAPEX):An Interdisciplinary and Systems Approach towards Understanding Thoracic Aortic Disease

Current management guidelines for ascending thoracic aortic aneurysms (aTAA) recommend intervention once ascending or sinus diameter reaches 5–5.5 cm or shows a growth rate of &gt;0.5 cm/year estimated from echo/CT/MRI. However, many aTAA dissections (aTAAD) occur in vessels with diameters below the surgical intervention threshold of &lt;55 mm. Moreover, during aTAA repair surgeons observe and experience considerable variations in tissue strength, thickness, and stiffness that appear not fully explained by patient risk factors. To improve the understanding of aTAA pathophysiology, we established a multi-disciplinary research infrastructure: The Maastricht acquisition platform for studying mechanisms of tissue–cell crosstalk (MAPEX). The explicit scientific focus of the platform is on the dynamic interactions between vascular smooth muscle cells and extracellular matrix (i.e., cell–matrix crosstalk), which play an essential role in aortic wall mechanical homeostasis. Accordingly, we consider pathophysiological influences of wall shear stress, wall stress, and smooth muscle cell phenotypic diversity and modulation. Co-registrations of hemodynamics and deep phenotyping at the histological and cell biology level are key innovations of our platform and are critical for understanding aneurysm formation and dissection at a fundamental level. The MAPEX platform enables the interpretation of the data in a well-defined clinical context and therefore has real potential for narrowing existing knowledge gaps. A better understanding of aortic mechanical homeostasis and its derangement may ultimately improve diagnostic and prognostic possibilities to identify and treat symptomatic and asymptomatic patients with existing and developing aneurysms.</p

No accelerated arterial aging in relatively young women after preeclampsia as compared to normotensive pregnancy

IntroductionPreeclampsia, an endothelial disorder of pregnancy, predisposes to remote cardiovascular diseases (CVD). Whether there is an accelerated effect of aging on endothelial decline in former preeclamptic women is unknown. We investigated if the arterial aging regarding endothelial-dependent and -independent vascular function is more pronounced in women with a history of preeclampsia as compared to women with a history of solely normotensive gestation(s).MethodsData was used from the Queen of Hearts study (ClinicalTrials.gov Identifier NCT02347540); a large cross-sectional study on early detection of cardiovascular disease among young women (≥18 years) with a history of preeclampsia and a control group of low-risk healthy women with a history of uncomplicated pregnancies. Brachial artery flow-mediated dilation (FMD; absolute, relative and allometric) and sublingually administered nitroglycerine-mediated dilation (NGMD; absolute and relative) were measured using ultrasound. Cross-sectional associations of age with FMD and NGMD were investigated by linear regression. Models were adjusted for body mass index, smoking, antihypertensive drug use, mean arterial pressure, fasting glucose, menopausal state, family history of CVD and stress stimulus during measurement. Effect modification by preeclampsia was investigated by including an interaction term between preeclampsia and age in regression models.ResultsOf the 1,217 included women (age range 22–62 years), 66.0% had a history of preeclampsia and 34.0% of normotensive pregnancy. Advancing age was associated with a decrease in relative FMD and NGMD (unadjusted regression coefficient: FMD: −0.48%/10 years (95% CI:−0.65 to −0.30%/10 years), NGMD: −1.13%/10 years (−1.49 to −0.77%/10 years)) and increase in brachial artery diameter [regression coefficient = 0.16 mm/10 years (95% CI 0.13 to 0.19 mm/10 years)]. Similar results were found when evaluating FMD and NGMD as absolute increase or allometrically, and after confounder adjustments. These age-related change were comparable in former preeclamptic women and controls (p-values interaction ≥0.372). Preeclampsia itself was independently associated with consistently smaller brachial artery diameter, but not with FMD and NGMD.ConclusionIn young- to middle-aged women, vascular aging in terms of FMD and NGMD was not accelerated in women after preeclampsia compared to normotensive pregnancies, even though former preeclamptic women consistently have smaller brachial arteries

Associations of Arterial Stiffness With Cognitive Performance, and the Role of Microvascular Dysfunction:The Maastricht Study

The mechanisms underlying cognitive impairment are incompletely understood but may include arterial stiffness and microvascular dysfunction. In the population-based Maastricht Study, we investigated the association between arterial stiffness and cognitive performance, and whether any such association was mediated by microvascular dysfunction. We included cross-sectional data of 2544 participants (age, 59.7 years; 51.0% men; 26.0% type 2 diabetes mellitus). We used carotid-femoral pulse wave velocity and carotid distensibility coefficient as measures of aortic and carotid stiffness, respectively. We calculated a composite score of microvascular dysfunction based on magnetic resonance imaging features of cerebral small vessel disease, flicker light-induced retinal arteriolar and venular dilation response, albuminuria, and plasma biomarkers of microvascular dysfunction (sICAM-1 [soluble intercellular adhesion molecule-1], sVCAM-1 [soluble vascular adhesion molecule-1], sE-selectin [soluble E-selectin], and vWF [von Willebrand factor]). Cognitive domains assessed were memory, processing speed, and executive function. A cognitive function score was calculated as the average of these domains. Higher aortic stiffness (per m/s) was associated with lower cognitive function (β, -0.018 SD [95% CI, -0.036 to -0.000]) independent of age, sex, education, and cardiovascular risk factors, but higher carotid stiffness was not. Higher aortic stiffness (per m/s) was associated with a higher microvascular dysfunction score (β, 0.034 SD [95% CI, 0.014 to 0.053]), and a higher microvascular dysfunction score (per SD) was associated with lower cognitive function (β, -0.089 SD [95% CI, -0.124 to -0.053]). Microvascular dysfunction significantly explained 16.2% of the total effect of aortic stiffness on cognitive function. The present study showed that aortic stiffness, but not carotid stiffness, is independently associated with worse cognitive performance, and that this association is in part explained by microvascular dysfunction

Carotid stiffness is associated with impairment of cognitive performance in individuals with and without type 2 diabetes. The Maastricht Study

AbstractBackground and aimsThere is increasing evidence linking arterial (mainly aortic) stiffness and type 2 diabetes, a risk factor for arterial stiffness, to cognitive impairment and dementia. However, data on carotid stiffness, which may be especially relevant for cognitive performance, are scarce, and few studies have addressed the interplay between arterial stiffness, type 2 diabetes, and cognitive performance.MethodsWe studied individuals with (n = 197) and without (n = 528) type 2 diabetes, who completed a neuropsychological test battery and underwent applanation tonometry and vascular ultrasound to evaluate aortic (i.e. carotid-to-femoral pulse wave velocity) and carotid stiffness (i.e. distensibility, compliance and Young's elastic modulus). Linear regression analyses were performed and adjusted for demographics, vascular risk factors, and depression.ResultsOverall, our results showed that carotid, but not aortic, stiffness was associated with worse cognitive performance, primarily in the domains of processing speed (standardized regression coefficient for distensibility −0.083, p = 0.040; compliance −0.077, p = 0.032) and executive function and attention (distensibility −0.133, p = 0.001; compliance −0.090, p = 0.015; Young's elastic modulus −0.081, p = 0.027). These associations did not differ by diabetes status. The differences in cognitive performance between individuals with and without type 2 diabetes (mean difference in domain scores relative to those without diabetes for free recall memory −0.23, processing speed −0.19, executive function and attention −0.23; all p ≤ 0.009 and adjusted for demographics, traditional vascular risk factors, and depression) were not substantially altered after additional adjustment for carotid stiffness.ConclusionsOur findings suggest that carotid stiffness is associated with cognitive performance in both individuals with and without diabetes, but does not mediate the relationship between type 2 diabetes and cognitive dysfunction

Pleiotropic Benefit of Monomeric and Oligomeric Flavanols on Vascular Health - A Randomized Controlled Clinical Pilot Study

BACKGROUND: Cardiovascular diseases are expanding to a major social-economic burden in the Western World and undermine man's deep desire for healthy ageing. Epidemiological studies suggest that flavanol-rich foods (e.g. grapes, wine, chocolate) sustain cardiovascular health. For an evidenced-based application, however, sound clinical data on their efficacy are strongly demanded. METHODS: In a double-blind, randomized, placebo-controlled intervention study we supplemented 28 male smokers with 200 mg per day of monomeric and oligomeric flavanols (MOF) from grape seeds. At baseline, after 4 and 8 weeks we measured macro- and microvascular function and a cluster of systemic biomarkers for major pathological processes occurring in the vasculature: disturbances in lipid metabolism and cellular redox balance, and activation of inflammatory cells and platelets. RESULTS: In the MOF group serum total cholesterol and LDL decreased significantly (P ≤ 0.05) by 5% (n = 11) and 7% (n = 9), respectively in volunteers with elevated baseline levels. Additionally, after 8 weeks the ratio of glutathione to glutathione disulphide in erythrocytes rose from baseline by 22% (n = 15, P<0.05) in MOF supplemented subjects. We also observed that MOF supplementation exerts anti-inflammatory effects in blood towards ex vivo added bacterial endotoxin and significantly reduces expression of inflammatory genes in leukocytes. Conversely, alterations in macro- and microvascular function, platelet aggregation, plasma levels of nitric oxide surrogates, endothelin-1, C-reactive protein, fibrinogen, prostaglandin F2alpha, plasma antioxidant capacity and gene expression levels of antioxidant defense enzymes did not reach statistical significance after 8 weeks MOF supplementation. However, integrating all measured effects into a global, so-called vascular health index revealed a significant improvement of overall vascular health by MOF compared to placebo (P ≤ 0.05). CONCLUSION: Our integrative multi-biomarker approach unveiled the pleiotropic vascular health benefit of an 8 weeks supplementation with 200 mg/d MOF in humans. TRIAL REGISTRATION: ClinicalTrials.gov NCT00742287