Blood pressure and arterial stiffness indices in 5-years follow-up

Wstęp Spośród nieinwazyjnych parametrów oceny dużych naczyń tętniczych, wartości ciśnienia tętna (PP) i wskaźnika wzmocnienia (AI) fali tętna mają znaczenie prognostyczne. Celem badania była ocena zmiany ciśnienia tętniczego (BP) i AI w 5-letniej obserwacji. Materiał i metody Badaniem objęto 197 osób z losowo wybranych rodzin (99 rodziców i 98 ich dorosłych potomków w wieku na początku badania odpowiednio średnio 51,4 i 25,5 roku), w tym 110 osób z prawidłowym BP i 87 z nadciśnieniem. Wyjściowo i po okresie obserwacji wynoszącym 4,8 &#177; 0,3 roku, BP mierzono sfigmomanometrem rtęciowym, rejestrowano falę tętna przy zastosowaniu tonometrii aplanacyjnej (SphygmoCor, PWV Medical, Australia). Oceniano obwodowy wskaźnik wzmocnienia (PAI) i centralny wskaźnik wzmocnienia (CAI) oraz PP. Poziom istotności statystycznej dla różnic między grupami w zakresie zmian badanych parametrów w trakcie obserwacji oceniano przy zastosowaniu regresji liniowej z uwzględnieniem wartości wyjściowych. Wyniki Zarówno w grupie rodziców, jak i dorosłych dzieci, jak również u osób z prawidłowym BP i nadciśnieniem w obserwacji odległej stwierdzono porównywalny wzrost wskaźnika masy ciała (BMI) i spadek częstości akcji serca. Obserwowano większy wzrost centralnego skurczowego ciśnienia tętniczego (CSBP) z mniejszym spadkiem centralnego rozkurczowego ciśnienia tętniczego (CDBP) w pokoleniu potomków i wśród osób z prawidłowym BP przy istotniejszym wzroście wartości centralnego ciśnienia tętna (CPP) w pokoleniu rodziców i osób z nadciśnieniem (p < 0,005). Podobnie, obserwowano większy wzrost obwodowego skurczowego ciśnienia tętniczego (PSBP), a w związku z tym mniejszą redukcję rozkurczowego ciśnienia (PDBP) z porównywalną zmianą wartości obwodowego ciśnienia tętna (PPP) w pokoleniu potomków i u osób z prawidłowym BP. Zmiany wartości PAI i CAI były bardziej zaznaczone w młodszym pokoleniu w porównaniu z pokoleniem rodziców i wyniosły odpowiednio 4,4 v. 2,9%; p = 0,004 i 5,2 v. 3,7%; p = 0,0001. Ponadto zaobserwowano większy wzrost PAI (4,6 v. 4,3%; p = 0,006) i CAI (4,8 v. 4,6%; p = 0,005) u osób z nadciśnieniem w porównaniu z osobami z prawidłowym BP. Wnioski Aortalne ciśnienie tętna jest czulszym wskaźnikiem usztywnienia aorty związanego z wiekiem i BP niż PPP. Wyniki badania wskazują, że AI istotnie wzrasta w pokoleniu potomków, co potwierdza jego przydatność w ocenie progresji sztywności aorty u młodych osób. Nadciśnienie Tętnicze 2010, tom 14, nr 6, strony 443-450Background Augmentation index (AI) a measure of enhanced wave reflection and pulse pressure have been proposed as a bedside measure of aortic stiffness. The objective of the present study was to assess changes in blood pressure (BP) parameters and AI in general population after 5-years follow-up. Material and methods From the general population we recruited 197 members from random families (99 parents and 98 offspring [age at baseline: 51.4 and 25.5 years] who constituted 110 normotensives and 87 hypertensives). Initially and after mean follow-up 4.8 &#177; 0.3 years we recorded the radial arterial waveform using the SphygmoCor device. We evaluated peripheral AI (PAI) and central AI (CAI). Significance levels of betweengroup comparisons of the change from baseline were assessed by a general linear model that adjusted for baseline value. Results In both generations as well as in normo- and hypertensive groups we observed comparable increase in BMI and decrease in heart rate. We found higher increase in aortic SBP with lesser decrease in central DBP in offspring and in normotensives while CPP increase was higher in parents and in participants with initially diagnosed hypertension (p < 0.005). We observed greater elevation of brachial SBP with simultaneous lesser reduction in DBP with similar increase in peripheral PP in offspring and in normotensives. Changes in PAI and CAI were more pronounced in younger generation and resulted respectively 4.4 vs 2.9%; p = 0.004 and 5.2 vs 3.7%; p = 0.0001. Moreover we observed higher increase in PAI (4.6 vs 4.3%; p = 0.006) and in CAI (4.8 vs 4.6%; p = 0.005) in hypertensives. Conclusions The aortic pulse pressure more effectively indicate age and blood pressure related changes in arterial wall stiffening than brachial pressure. Our findings indicate that AI increased in offspring and can be used as effective tool to detect the progressive increase in aortic stiffness in younger individuals. Arterial Hypertension 2010, vol. 14, no 6, pages 443-45

Biomechanics of common carotid arteries from mice heterozygous for mgR, the most common mouse model of Marfan syndrome

Marfan syndrome, affecting approximately one out of every 5,000 people, is characterized by abnormal bone growth, ectopia lentis, and often-fatal aortic dilation and dissection. The root cause is a faulty extracellular matrix protein, fibrillin-1, which associates with elastin in many tissues. Common carotids from wild-type controls and mice heterozygous for the mgR mutation, the most commonly used mouse model of Marfan syndrome, were studied in a biaxial testing device. Mechanical data in the form of pressure-diameter and force-stretch tests in both the active and passive states were collected, as well data on the functional responses to phenylephrine, carbamylcholine chloride, and sodium nitroprusside. Although little significant difference was found between the heterozygous and wild-type groups in general, the in vivo stretch for both groups was significantly different from previously studied mouse vessels. Although the two groups do not exhibit significant differences, this study comprises a control group for future work with mice homozygous for mgR, which do exhibit Marfan-like symptoms. As treatment of Marfan syndrome improves, more Marfan patients will survive and age, increasing the likelihood that they will develop many of the vascular complications affecting the normal population, including hypertension and atherosclerosis. Therefore, it is imperative to gather biomechanical data from the Marfan vasculature so that clinicians may predict the effects of vascular complications in Marfan patients and develop appropriate methods of treatment

Biomechanics of common carotid arteries from mice heterozygous for mgR, the most common mouse model of Marfan syndrome

Marfan syndrome, affecting approximately one out of every 5,000 people, is characterized by abnormal bone growth, ectopia lentis, and often-fatal aortic dilation and dissection. The root cause is a faulty extracellular matrix protein, fibrillin-1, which associates with elastin in many tissues. Common carotids from wild-type controls and mice heterozygous for the mgR mutation, the most commonly used mouse model of Marfan syndrome, were studied in a biaxial testing device. Mechanical data in the form of pressure-diameter and force-stretch tests in both the active and passive states were collected, as well data on the functional responses to phenylephrine, carbamylcholine chloride, and sodium nitroprusside. Although little significant difference was found between the heterozygous and wild-type groups in general, the in vivo stretch for both groups was significantly different from previously studied mouse vessels. Although the two groups do not exhibit significant differences, this study comprises a control group for future work with mice homozygous for mgR, which do exhibit Marfan-like symptoms. As treatment of Marfan syndrome improves, more Marfan patients will survive and age, increasing the likelihood that they will develop many of the vascular complications affecting the normal population, including hypertension and atherosclerosis. Therefore, it is imperative to gather biomechanical data from the Marfan vasculature so that clinicians may predict the effects of vascular complications in Marfan patients and develop appropriate methods of treatment

The hypotensive effects of conventional non-fat dairy products : the role of arterial stiffness

textHigh consumption of dairy products, particularly non-fat dairy, is associated with reduced risk of high blood pressure and vascular dysfunction. Currently, it is not known if the solitary addition of conventional non-fat dairy products to the normal routine diet is capable of reducing blood pressure or improving vascular function. Accordingly, the primary aims of the present study were to determine if the solitary addition of conventional non-fat dairy products to the normal routine diet would reduce blood pressure and improve vascular function in middle-aged and older adults with elevated blood pressure. Using a randomized, crossover intervention study design, forty-nine adults with elevated blood pressure underwent a High Dairy condition (+4 servings/day of conventional non-fat dairy products) and isocaloric No Dairy condition (+4 servings/day fruit products) in which all dairy products were removed. Both dietary conditions lasted 4 weeks with a 2-week washout before crossing over into the alternate condition. In Study 1, the High Dairy condition produced reductions in brachial systolic blood pressure and pulse pressure. The hypotensive effects were observed within three weeks after the initiation of dietary intervention and in both casual seated and ambulatory (24-hour) measurements. On the contrary, pulse pressure was increased after removal of all dairy products in the No Dairy condition compared to baseline and after in the High Dairy condition. There were no changes in diastolic blood pressure after either dietary condition. In Study 2, the High Dairy condition produced reductions in carotid systolic blood pressure, pulse pressure, and carotid-femoral pulse wave velocity with a concomitant increase in brachial flow-mediated dilation and cardiovagal baroreflex sensitivity. Brachial flow-mediated dilation decreased and carotid pulse pressure increased after removal of all dairy products in the No Dairy condition. Furthermore, [delta] carotid systolic blood pressure and carotid-femoral pulse wave velocity were highly related. Taken together, we concluded that the solitary manipulation of conventional dairy products, particularly non-fat dairy, in the normal routine diet would modulate levels of blood pressure and vascular function in middle-aged and older adults with pre-hypertension and hypertension.Kinesiology and Health Educatio

Multiscale Modeling of Hemodynamics in Human Vessel Network and Its Applications in Cerebral Aneurysms

Three-dimensional (3D) simulation of patient-specific morphological models has been widely used to provide the hemodynamic information of individual patients, such as wall shear stress (WSS), oscillatory shear index (OSI), and flow patterns, etc. Since patient-specific morphological segment was only restricted locally, boundary conditions (BCs) are required to implement the CFD simulation. Direct measurements of the flow and pressure waveforms were often required as input BCs for 3D CFD simulations of patient-specific models. However, as the morphology develops, the feedback from this topological deformation may lead to BCs being altered, and hence without this feedback, the flow characteristics of the morphology are only computed locally. A one-dimensional (1D) numerical model containing the entire human vessel network has been proposed to compute the global hemodynamics. In the meantime, experimental studies of blood flow in the patient-specific modeling of the circle of Willies (CoW) was conducted. The flow and pressure waveforms were quantified to validate the accuracy of the pure 1D model. This 1D model will be coupled with a 3D morphological model to account for the effects of the altered BCs. The proposed 1D-3D multi-scale modeling approach investigates how the global hemodynamic changes can be induced by the local morphological effects, and in consequence, may further result in altering of BCs to interfere with the solution of the 3D simulation. Validation of the proposed multi-scale model has also been made by comparing the solution of the flow rate and pressure waveforms with the experimental data and 3D numerical simulations reported in the literature. Moreover, the multi-scale model is extended to study a patient-specific cerebral aneurysm and a stenosis model. The proposed multi-scale model can be used as an alternative to current approaches to study intracranial vascular diseases such as an aneurysm, stenosis, and combined cases

Impact of arterial stiffness on white matter microstructure in the elderly

La rigidité artérielle fait référence à la perte d'élasticité principalement dans les grandes artères telles que l'aorte et les carotides. On sait que la rigidité artérielle chroniquement élevée contribue à des modifications vasculaires cérébrales telles que des lésions parenchymateuses de la substance blanche cérébrale via une modification du flux sanguin cérébral. En particulier, parmi les structures perfusées par les artérioles fournies par les artères cérébrales antérieure et moyenne, le corps calleux, la capsule interne, la corona radiata et le faisceau longitudinal supérieur sont les plus vulnérables à l’hypoperfusion. Des études antérieures ont montré que l'augmentation de la rigidité artérielle évaluée par la vitesse de l'onde de pouls carotide-fémorale (cfPWV) est associée à une diminution de l'anisotropie fractionnelle (FA) et à une augmentation de la diffusivité radiale (RD). On a émis l'hypothèse que les altérations au niveau des régions vulnérables de la substance blanche (par exemple, le corps calleux, la capsule interne) seraient probablement liées à la démyélinisation axonale. Cependant, bien que la RD a auparavant été corrélée avec la démyélinisation axonale, l'imagerie de diffusion est principalement aveugle à la myéline. En revanche, l'imagerie par transfert de magnétisation (MT) est une métrique adaptée pour estimer la fraction volumique de myéline. De plus, malgré leur sensibilité à l'organisation des fibres axonales, les métriques de tenseur de diffusion (DTI) telles que les FA et RD manquent de spécificité pour la microstructure tissulaire individuelle. Des modèles microstructuraux plus avancés tels que l’imagerie dispersion et de l'orientation des neurites (NODDI) fournissent des outils pour disséquer les changements microstructuraux derrière les mesures DTI. Dans l'article 1, nous avons utilisé les métriques de DTI et basé sur le MT pour examiner de plus près l'interaction entre la rigidité artérielle et la microstructure de la substance blanche chez les personnes âgées de plus de 65 ans. Nous avons constaté que la mesure de référence absolue de la rigidité artérielle, la mesure de la vitesse de l'onde de pouls entre l’artère fémorale et carotidienne (cfPWV) était associée à l'organisation axonale des fibres telle que reflétée par FA et RD plutôt qu'à la démyélinisation dans les régions de la substance blanche qui ont été précédemment désignées comme vulnérables à rigidité artérielle. Dans notre deuxième article, nous avons utilisé le modèle NODDI pour approfondir la relation entre le cfPWV et l'organisation axonale. Nos résultats ont montré que la cfPWV est positivement associée à la diffusion extracellulaire de l'eau (ISOVF), ce qui signifie que la rigidité artérielle peut entraîner une dispersion axonale, diminuant la contrainte de directionnalité de l'eau le long des axones. En outre, nous avons constaté que la rigidité artérielle est associée à une augmentation de la densité des fibres dans le corps calleux tel que mesuré par l’ICVF, ce qui pourrait suggérer que les personnes à risque plus élevé de déclin cognitif présentent des mécanismes compensatoires précoces avant l'apparition de signes cliniques de déclin cognitif. Compte tenu de la forte interaction entre la rigidité artérielle et le déclin à la fois de la structure du cerveau et des fonctions cérébrales, on peut envisager un avenir meilleur où la rigidité artérielle sera mesurée dans la pratique clinique de routine afin d'identifier les personnes à risque plus élevé d’altérations de la substance blanche et de déclin cognitif. Ces personnes pourraient bénéficier de programmes multi-interventionnels visant à préserver la structure et la fonction cérébrale. Un seuil de rigidité artérielle est donc nécessaire pour identifier ces individus. L'article 3 présente la première estimation d'une valeur seuil de cfPWV à laquelle la rigidité artérielle affecte la microstructure de la substance blanche chez les personnes âgées. Nos résultats suggèrent que le seuil actuel de 10 m / s de cfPWV adopté par la Société européenne d'hypertension n'est peut-être pas le seuil optimal pour diviser les individus en groupes à risque neurovasculaire élevé et faible. Au lieu de cela, nos résultats suggèrent que le seuil de cfPWV est plus susceptible d’être autour de 8,5 m / s. Bien que le cfPWV offre une excellente valeur pronostique chez les adultes, il reste malheureusement principalement utilisé dans la recherche en raison du besoin d'experts formés pour cette mesure. À l'inverse, la mesure de l'indice de rigidité artérielle (ASI) à l'aide de la pléthysmographie suscite un intérêt croissant ces dernières années en raison de son approche simple à utiliser. Dans l'article 4, nous avons étudié la relation entre l'ASI et la pression pulsée (PP) qui est une mesure indirecte de la rigidité artérielle, avec la FA et les lésions de la substance blanche chez les participants du UK Biobank. Nous avons constaté que la PP prédit mieux l'intégrité de la substance blanche que l'ASI chez les participants de moins de 75 ans. Cette constatation implique que l'ASI de la pléthysmographie ne semble pas être une mesure fiable de la rigidité artérielle chez les personnes âgées. Des études futures sont évidemment nécessaires pour valider nos résultats, en particulier notre seuil de cfPWV. Une fois ce seuil validé, nous envisageons un avenir radieux où la mesure du cfPWV sera non seulement utilisée pour aider à sélectionner les personnes qui bénéficieraient le plus d'un programme multi-interventionnel visant à préserver l'intégrité cérébrale, mais pourrait également être utilisée pour surveiller l’effet d’une telle intervention.Arterial stiffness refers to the loss of elasticity mainly in large arteries such as the aorta and carotids. Chronically elevated arterial stiffness contributes to cerebrovascular changes such as cerebral white matter parenchymal damage via an alteration of cerebral blood flow. In particular, among the areas perfused by arterioles supplied by the anterior and middle cerebral arteries, the corpus callosum, the internal capsule, the corona radiata, and the superior longitudinal fasciculus are more vulnerable to cerebral hypoperfusion. Previous studies have shown that increased arterial stiffness as assessed by carotid-femoral pulse wave velocity (cfPWV) is associated with a decrease in fractional anisotropy (FA) and increase in radial diffusivity (RD). It was hypothesized that alterations in vulnerable white matter tracts (e.g. corpus callosum, internal capsule) are likely to be related to axonal demyelination. However, while RD was previously correlated with axonal demyelination, diffusion imaging is mostly blind to myelin. In contrast magnetization transfer (MT) imaging is a tailored metric to estimate myelin volume fraction. Moreover, despite their sensitivity to axon fiber organization, diffusion tensor metrics (DTI) such as FA and RD lack specificity for individual tissue microstructure. More advanced microstructural model such as neurite orientation dispersion and density imaging (NODDI) give tools to disecate the microstructural changes behind DTI metrics. In Article 1 we used DTI and MT based metric to look more closely at the interplay between arterial stiffness and white matter microstructure in older adults > 65 years old. We found that the gold standard measure of arterial stiffness, the measure of carotid femoral pulse wave velocity (cfPWV) was associated with axonal fiber organization as reflected by FA and RD rather than demyelination in the white matter regions that have been previously denoted as vulnerable to arterial stiffness. In our second Article, we used the NODDI model to take a further look at the relationship between cfPWV and axonal organization. Our results showed that cfPWV is positively associated with the extracellular water diffusion (ISOVF) which means that arterial stiffness may result in axonal dispersion, lessening the constraint of water directionality along axons. In addition, we found that arterial stiffness is associated with increased fibers density in the corpus callosum as measured by ICVF which could suggest that individuals at higher risk for cognitive decline demonstrate early compensatory mechanisms before the appearance of clinical signs of cognitive decline. Considering the strong interplay between arterial stiffness and decline both in brain structure and function, one can envision a bright future where arterial stiffness would be measured in routine clinical practice in order to identify individuals at higher risk for white matter changes and cognitive decline. Such individuals could benefit from multi-interventions programs aiming to preserve brain structure and function. A cut-off arterial stiffness is thus needed to identify these individuals. Article 3 presents the first estimation of an cfPWV cut-off value at which arterial stiffness impacts the white matter microstructure in older adults. Our results suggested that the current 10 m/s cfPWV cut-off adopted by the European Society of Hypertension may not be the optimal threshold to split individuals into high and low neurovascular risk groups. Instead, our findings suggest that the cfPWV cut-off is more likely to fall around 8.5 m/s. While cfPWV provides excellent prognostic value in adults, it remains unfortunately mainly used in research due to the need of trained experts. Conversely, measure of arterial stiffness index (ASI) using plethysmography is getting increased interest in the last few years due to its simple-to-use approach. In article 4, we investigated the relationship between ASI and pulse pressure (PP), an indirect measure of arterial stiffness, with FA and white matter lesions in participants of the UK Biobank. We found that PP better predicts white matter integrity compared to ASI in participants younger than 75 years old. This finding implies that ASI from plethysmography may not be a reliable measure of arterial stiffness in older adults. Future studies are obviously needed to validate our results, in particular our cfPWV cut-off. Once such cut-off will be validated, the present author envision a bright future where measure of cfPWV will not only be used to help selecting individuals that would most benefit from a multi intervention program aiming to preserve brain integrity, but could also be used to monitor the effect of such intervention

Biomarcatori ecografici di funzione e struttura vascolare nell'uomo Imaging biomarkers of vascular function and structure in humans

Cardiovascular (CV) disease is the first cause of mortality and morbidity in the world. Prevention of this condition, which is responsible of more than 2200 deaths per day only in United States, is a public health priority. Thus in the last decades great efforts have been made in the search of non-invasive biomarkers, able to identify the individual at risk for CV events in the asymptomatic, subclinical stage. Some biomarkers are currently recommended in order to improve stratification of CV risk, whereas other are considered useful only for research purposes. In particular, increased intima-media thickness of the common carotid artery (C-IMT), representing a marker of early atherosclerosis significantly correlated with coronary or cerebrovascular disease, has been considered as an intermediate stage in the continuum of vascular disease and as a predictor of CV risk. Current guidelines also introduced other vascular parameters evaluating mechanical and functional arterial properties of peripheral and central arteries. Increased aortic stiffness has been shown to predict future CV events and it has been recognized as a marker of subclinical target organ damage in hypertensive patients. Earlier vascular abnormalities, such as endothelial dysfunction in the peripheral arteries, have been also mentioned for their possible use in future. However, several questions in this field are still open, limiting the wide use of these tools in the clinical practice. The open issues concern methodological as well as pathophysiological and prognostic aspects, and in this thesis we will discuss only a small part of these ones. First, C-IMT and arterial stiffness represent two sides of vascular aging, atherosclerosis and arteriosclerosis respectively, and are generally considered structural alterations. The identification of a “functional” component in these alterations would be of interest, since it will suggest a possibility of reversibility of vascular aging. Second, vascular aging is a process involving the whole organism, while different techniques explore different districts. The quantification of the impact of different CV risk factors on different vascular districts might indicate the most adequate biomarker to use for future studies and suggest specific mechanisms of disease in different conditions. Third, vascular aging is often accompanied by cardiac and renal damage, but the relationship between organ damage in different districts is still largely unexplored. Fourth, while hypertension and diabetes have become the main cause of end-stage renal disease, and chronic kidney disease has been recognized as a main cause of CV events, to date early markers of renal vascular damage have not been developed. For this PhD thesis I examined cross-sectionally a cohort of healthy subjects and patients with traditional CV risk factors in order to elucidate some of the abovementioned aspects. My original contribution to the knowledge in this field consists in: - the demonstration of a “functional” component in aortic stiffness, that is present only in diabetic patients and relies on endothelium-mediated mechanisms; - the demonstration of a differential impact of different CV risk factors on carotid and aortic stiffness; - the demonstration, in hypertensive patients, of an additive role of carotid and aortic stiffness in determining cardiac organ damage; - the identification of a new marker of renal vascular damage. In the second part of the PhD thesis, I sought to demonstrate the usefulness of imaging biomarkers of vascular function and structure not only for risk stratification in patients with traditional CV risk factors, but also to explore CV consequences of non primarily CV diseases and conditions. We hypothesized that a comprehensive, multiparametric approach would be the best strategy to detect early vascular damage in one or more districts, possibly in a subclinical, reversible stage. This approach could allow identifying the “CV footprint” characterizing each condition, with a double aim: to elucidate the pathophysiology of CV complications in non-CV diseases and to propose the most useful test to be used in the clinical practice for screening and follow-up. During my PhD thesis I applied this strategy to some primarily non-CV conditions that might qualify as emerging CV risk factors, such as exposure to environmental and iatrogenic radiation doses, obstructive sleep apnea syndrome (OSAS) in the absence of traditional CV risk factors, and chronic exposure to hypobaric hypoxia at high altitude. My original contribution to the knowledge in this field consisted in: - the demonstration of a selective reduction of circulating endothelial progenitor cells, in the presence of preserved vascular function and structure, in young adults exposed during childhood to environmental radiation doses after the Chernobyl disaster and to therapeutic radioiodine treatment after thyroid cancer; - the demonstration that conduit artery endothelial dysfunction and impaired renal vasodilating capacity are part of the vascular phenotype of OSAS per se, since they are present even in the absence of traditional CV risk factors, while structural alterations such as arterial stiffness and increased C-IMT characterized only obese and/or hypertensive OSAS patients; - the demonstration that Himalayan high altitude dwellers, chronically living above 2500 meters of altitude, present a mainly microcirculatory endothelial dysfunction and a maladaptive carotid remodeling even in the absence of traditional CV risk factors

Senescence

The book "Senescence" is aimed to describe all the phenomena related to aging and senescence of all forms of life on Earth, i.e. plants, animals and the human beings. The book contains 36 carefully reviewed chapters written by different authors, aiming to describe the aging and senescent changes of living creatures, i.e. plants and animals