Assessing hemodynamics from the photoplethysmogram to gain insights into vascular age: A review from VascAgeNet

The photoplethysmogram (PPG) signal is widely measured by clinical and consumer devices, and it is emerging as a potential tool for assessing vascular age. The shape and timing of the PPG pulse wave are both influenced by normal vascular ageing, changes in arterial stiffness and blood pressure, and atherosclerosis. This review summarises research into assessing vascular age from the PPG. Three categories of approaches are described: (i) those which use a single PPG signal (based on pulse wave analysis); (ii) those which use multiple PPG signals (such as pulse transit time measurement); and (iii) those which use PPG and other signals (such as pulse arrival time measurement). Evidence is then presented on the performance, repeatability and reproducibility, and clinical utility of PPG-derived parameters of vascular age. Finally, the review outlines key directions for future research to realise the full potential of photoplethysmography for assessing vascular age.

Early Vascular Aging in Children With Type 1 Diabetes and Ambulatory Normotension

Background: Preliminary data suggest that target organ damage (TOD) and early vascular aging (EVA) may occur in children with normal blood pressure (BP).Objectives: To analyze TOD and EVA in normotensive (BP <95th percentile on ambulatory BP monitoring) type 1 diabetes children (T1D) in comparison to healthy controls (C).Subjects: 25 T1D aged 13.9 ± 2.6 years and 22 C aged 14.0 ± 3.4 years.Methods: We analyzed age- and height-related pulse wave velocity (PWV) Z-scores and expected PWV based on age, height, and mean arterial pressure (MAP). Expected vascular age based on measured PWV was calculated from pooled pediatric and adult PWV norms. Left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR), and urinary albumin/creatinine ratio (ACR) were obtained as markers of TOD.Results: T1D and C groups did not differ in anthropometry, ambulatory, LVMI, and ACR. However, median age- and height-related PWV Z-scores were higher in T1D compared to C (1.08 vs. 0.57, p = 0.006; 0.78 vs. 0.36, p = 0.02, respectively). Mean (±SD) difference between measured and expected PWV was 0.58 ± 0.57 in T1D vs. 0.22 ± 0.59 in C, p = 0.02. The mean (±SD) difference between chronological and expected vascular age was 7.53 ± 7.74 years in T1D vs. 2.78 ± 7.01 years in C, p = 0.04.Conclusion: Increased arterial stiffness and increased intraindividual differences between expected and measured PWV as well as between chronological and expected vascular age indicate that EVA may develop in T1D children even at normal ambulatory BP levels.

EVALUATION OF THE VESSEL AGE BY APPLYING THE ACCELERATION PLETHYSMOGRAM ANALYSIS

В работе приведены понятия жесткости, эластичности и тонуса сосудов, а также же их взаимосвязь с общим состоянием сосудистой стенки. Описан индекс, объединяющий влияние вышеперечисленных факторов на состояние сосудистой системы и дающий представление о возрасте сосудов пациента, а также показана связь этого индекса с возрастом человека. Представлен обзор способов определения возраста сосудов с помощью контурного анализа пульсовой волны. Среди предложенных способов был выделен подход на основе контурного анализа сигнала пульсовой волны, а также ее второй производной. В данном исследовании проводилась разработка алгоритма расчета показателя возраста сосудов (VA), базирующаяся на анализе сигнала и его второй производной. При этом особое внимание уделялось физической интерпретации параметров, входящих в состав расчетной формулы. С помощью представленного алгоритма в группе из трех испытуемых был определен сосудистый возраст. Из анализа полученных результатов было выявлено влияние физиологических факторов на значение возраста сосудов. Предложены методики, позволяющие исключить влияние этих факторов на значения показателя VA и тем самым получить более точные результаты. Также представлены стратегии дальнейшего развития исследований в этом направлении In The paper presents the concepts of rigidity, elasticity and tone of blood vessels, as well as their relationship with the general state of the vascular wall. An index is described that combines the influence of the above factors on the state of the vascular system and gives an idea of the age of the patient's vessels, and also shows the relationship of this index with the age of a person. An overview of the methods for determining the age of blood vessels using the contour analysis of the pulse wave is presented. Among the proposed methods, an approach based on the contour analysis of the pulse wave signal, as well as its second derivative, was singled out. In this study, an algorithm was developed for calculating the indicator of vascular age (VA), based on the analysis of the signal and its second derivative. In this case, special attention was paid to the physical interpretation of the parameters included in the calculation formula. Using the presented algorithm, vascular age was determined in a group of three subjects. From the analysis of the results obtained, the influence of physiological factors on the value of the age of the vessels was revealed. Methods are proposed that allow to exclude the influence of these factors on the values of the VA indicator and thereby obtain more accurate results. Also presented are strategies for the further development of research in this direction

Vascular ageing and peripheral pulse: an improved model for assessing their relationship

Objective:Vascular ageing is associated with several alterations, including arterial stiffness and endothelial dysfunction. Such alterations represent an independent factor in the development of cardiovascular disease. In our previous works we demonstrated the alterations occurring in the vascular system are themselves reflected in the shape of the peripheral waveform; thus, a model that describes the waveform as a sum of Gaussian curves provides a set of parameters that successfully discriminate between under(<= 35 years old) and over subjects (> 35 years old). In the present work, we explored the feasibility of a new decomposition model, based on a sum of exponential pulses, applied to the same problem. Approach: The first processing step extracts each pulsation from the input signal and removes the long-term trend using a cubic spline with nodes between consecutive pulsations. After that, a Least Squares fitting algorithm determines the set of optimal model parameters that best approximates each single pulse. The vector of model parameters gives a compact representation of the pulse waveform that constitutes the basis for the classification step. Each subject is associated to his/her "representative" pulse waveform, obtained by averaging the vector parameters corresponding to all pulses. Finally, a Bayesan classifier has been designed to discriminate the waveforms of under and over subjects, using the leave-one-subject-out validation method. Main results: Results indicate that the fitting procedure reaches a rate of 96% in under subjects and 95% in over subjects and that the Bayesan classifier is able to correctly classify 91\% of the subjects with a specificity of 94% and a sensibility of 84%. Significance: This study shows a sensible vascular age estimation accuracy with a multi-exponential model, which may help to predict cardiovascular diseases.

Leveraging the potential of machine learning for assessing vascular ageing: state-of-the-art and future research

Vascular ageing biomarkers have been found to be predictive of cardiovascular risk independently of classical risk factors, yet are not widely used in clinical practice. In this review we present two basic approaches for using machine learning (ML) to assess vascular age: parameter estimation and risk classification. We then summarize their role in developing new techniques to assess vascular ageing quickly and accurately. We discuss the methods used to validate ML-based markers, the evidence for their clinical utility, and key directions for future research. The review is complemented by case studies of the use of ML in vascular age assessment which can be replicated using freely available data and code.

Inhibitors of the sodium-glucose transporter type 2 and new possibilities for managing vascular age in patients with type 2 diabetes mellitus

The article discusses the pathophysiological mechanisms of the development of vascular aging as a combination of the influence on the body of genetic, environmental, regulatory, metabolic and other factors causing biochemical, enzymatic and cellular changes in the arterial vascular bed. The concept of “early vascular aging” and “healthy vascular aging” is defined depending on the ratio of the biological and chronological age of the vessels. The role of diabetes mellitus in increasing vascular stiffness, early vascular aging, as well as the progression of atherosclerotic cardiovascular diseases and their complications is considered in detail. Approaches to multifactorial management of vascular age in patients with type 2 diabetes (lifestyle modification with strategy of aggressive treatment of modifiers of atherosclerosis, rejection of bad habits, adherence to dietary recommendations and the use of modern organo- and vasoprotective antidiabetic drugs) are revealed. The mechanism of realization of vasoprotective effects of inhibitors of sodium-glucose transporter-2 (iNGLT-2) is described in detail. The results of completed large random ized trials EMPA-REG Outcome and EMPA-REG BP of the most studied representative of the IGLT-2 group, empagliflozin, are presented. It has been shown that due to their glucose and natriuretic effects, the ability to reduce body weight and blood pressure, improve myocardial metabolism and bioenergetics, decrease the activity of the sympathetic nervous system, as well as positive effects on vascular stiffness, NGLT-2 inhibitors are the drugs of choice in patients with type 2 diabetes mellitus (T2DM) and cardiovascular diseases. This makes it possible to widely use this group of drugs for managing the vascular age of patients and represents a new opportunity in the prevention of vascular aging in T2DM.

Opioids Cause Sex-Specific Vascular Changes via Cofilin-Extracellular Signal-Regulated Kinase Signaling: Female Mice Present Higher Risk of Developing Morphine-Induced Vascular Dysfunction than Male Mice

Recent studies have shown that chronic use of prescription or illicit opioids leads to an increased risk of cardiovascular events and pulmonary arterial hypertension. Indices of vascular age and arterial stiffness are also shown to be increased in opioid-dependent patients, with the effects being more marked in women. There are currently no studies investigating sex-specific vascular dysfunction in opioid use, and the mechanisms leading to opioid-induced vascular damage remain unknown. We hypothesized that exposure to exogenous opioids causes sex-specific vascular remodeling that will be more pronounced in female. Acknowledging the emerging roles of cofilins and extracellular signal-regulated kinases (ERKs) in mediating actin dynamics, we investigated the effects of morphine on these molecules. Twenty-four hour exposure to morphine increased inactivated cofilin and activated ERKs in resistance arteries from female mice, which may promote stress fiber over-assembly. We also performed continuous intraluminal infusion of morphine in pressurized resistance arteries from male and female mice using culture pressure myographs. We observed that morphine reduced the vascular diameter in resistance arteries from female, but not male mice. These results have significant implications for the previously unexplored role of exogenous opioids as a modifiable cardiovascular risk factor, especially in women.

Functional versus morphological assessment of vascular age in patients with coronary heart disease

Communicating cardiovascular risk based on individual vascular age (VA) is a well acknowledged concept in patient education and disease prevention. VA may be derived functionally, e.g. by measurement of pulse wave velocity (PWV), or morphologically, e.g. by assessment of carotid intima-media thickness (cIMT). The purpose of this study was to investigate whether both approaches produce similar results. Within the context of the German subset of the EUROASPIRE IV survey, 501 patients with coronary heart disease underwent (a) oscillometric PWV measurement at the aortic, carotid-femoral and brachial-ankle site (PWVao, PWVcf, PWVba) and derivation of the aortic augmentation index (AIao); (b) bilateral cIMT assessment by high-resolution ultrasound at three sites (common, bulb, internal). Respective VA was calculated using published equations. According to VA derived from PWV, most patients exhibited values below chronological age indicating a counterintuitive healthier-than-anticipated vascular status: for VAPWVao in 68% of patients; for VAAIao in 52% of patients. By contrast, VA derived from cIMT delivered opposite results: e.g. according to VAtotal-cIMT accelerated vascular aging in 75% of patients. To strengthen the concept of VA, further efforts are needed to better standardise the current approaches to estimate VA and, thereby, to improve comparability and clinical utility.