Vascular Aging Process Research Articles

Race/Ethnicity, Vascular Aging, and Mortality Risk: Evidence from the Health and Retirement Study

Vascular aging, which is associated with cardiovascular disease risk and mortality, is characterized by increasing arterial stiffness. The gold standard method for the assessment of arterial stiffness is carotid-femoral Pulse Wave Velocity (cfPWV). An emerging body of research suggests that cfPWV can be reasonably estimated from two commonly measured clinical variables—age and blood pressure. Thus, estimated Pulse Wave Velocity (ePWV) holds promise as a novel and easily obtained measure of arterial stiffness that can be used to study vascular aging, particularly with nationally representative datasets that collect biomarker data on sufficiently large sample sizes to examine race/ethnic differences. This analysis uses data from the 2006-2016 Health and Retirement Study to examine race/ethnic variation in the relationship between ePWV and mortality risk. We estimate logistic regression models predicting mortality over an eight-year period for four racial/ethnic groups: White, Black, Other, and Hispanic. Controls are included for sociodemographic characteristics, health status and behaviors, and blood biomarkers such as C-reactive protein, cystatin-C, hemoglobin A1c, total cholesterol and high-density lipoprotein (HDL) cholesterol. The results indicate ePWV increases the risk of mortality in the total sample and among each race/ethnic group, net the effect of age, systolic blood pressure, and diastolic blood pressure. Mechanisms that mediate this relationship are explored. The findings provide insight into vascular aging processes that influence mortality risk among race/ethnic groups.

Influencing factors of supernormal vascular aging in Chinese population.

Previous studies have analysed the epidemic characteristics of supernormal vascular aging (SUPERNOVA), and found that SUPERNOVA were significantly associated with lower risk of cardiovascular disease. However, the influencing factors of SUPERNOVA are still unclear. The aim of this study was to investigate the characteristics and influencing factors of SUPERNOVA. A total of 42 196 participants of the Kailuan Study were enrolled in the study. SUPERNOVA was defined as the lowest 2.5% of the age-quintile brachial-ankle pulse wave velocity (baPWV), early vascular aging was defined as the highest 2.5% of the age-quintile baPWV. Multivariable logistic regression analysis was applied to investigate the influencing factors of SUPERNOVA. The population with SUPERNOVA was mostly women, nonsmokers, nondrinkers, and those with higher education. They had lower levels of cardiovascular disease risk factors and healthier lifestyles. The results of logistics regression showed that the influencing factors of SUPERNOVA include age, sex, hypertension, diabetes, resting heart rate, hypersensitive C-reactive protein, and uric acid. However, the effects of these factors were different across age groups. We also observed that in addition to the unalterable factors (age and sex), only resting heart rate above 80 bpm (OR = 0.396, 95% CI: 0.231-0.681) and SBP (OR = 0.945, 95% CI: 0.932-0.958) were significantly associated with odds of SUPERNOVA in participants without cardiovascular risk factors. This study investigated the characteristics of the population with SUPERNOVA and the factors influencing it, which provided a basis for different populations to take preventive measures to slow down the process of vascular aging.

Lycopene ameliorates insulin resistance and increases muscle capillary density in aging via activation of SIRT1

Lycopene (Ly) is a kind of hydrocarbon, which belongs to the family of tetraterpene carotene and exists in red fruits and vegetables. The decrease of capillary density and blood flow with age is a significant reason for the increase of mortality and morbidity. Herein, our study aims to explore the effects of Ly (a bioactive food compound) on vascular aging in vitro and in vivo and its potential mechanisms. The cytological results showed that Ly could promote the proliferation of human umbilical vein endothelial cell (HUVECs) and enhance the ability of HUVECs to form capillary-like structures. Furthermore, the expression of SIRT1 in aged HUVECs was up-regulated. In vivo, aging rats showed signs of insulin resistance and blood vessel damage. Additionally, the capillary density and blood flow were reduced during the vascular aging process in both D‐gal‐induced and naturally aging muscle. However, when Ly was given, these conditions could be reversed. Simultaneously, the contents of ATP, lactic acid and pyruvic acid were determined, and it was found that Ly could promote angiogenesis by increasing the utilization rate of glucose and promoting energy metabolism. Finally, in the insulin resistance cell model, we knocked down the SIRT1 and administrated with Ly, and found that it couldn't restore insulin transdution. In conclusion, all the data in this study demonstrate that Ly could reactivate SIRT1 and improve insulin resistance, which was a reversible cause of vascular aging.

Roles and Mechanisms of DNA Methylation in Vascular Aging and Related Diseases.

Vascular aging is a pivotal risk factor promoting vascular dysfunction, the development and progression of vascular aging-related diseases. The structure and function of endothelial cells (ECs), vascular smooth muscle cells (VSMCs), fibroblasts, and macrophages are disrupted during the aging process, causing vascular cell senescence as well as vascular dysfunction. DNA methylation, an epigenetic mechanism, involves the alteration of gene transcription without changing the DNA sequence. It is a dynamically reversible process modulated by methyltransferases and demethyltransferases. Emerging evidence reveals that DNA methylation is implicated in the vascular aging process and plays a central role in regulating vascular aging-related diseases. In this review, we seek to clarify the mechanisms of DNA methylation in modulating ECs, VSMCs, fibroblasts, and macrophages functions and primarily focus on the connection between DNA methylation and vascular aging-related diseases. Therefore, we represent many vascular aging-related genes which are modulated by DNA methylation. Besides, we concentrate on the potential clinical application of DNA methylation to serve as a reliable diagnostic tool and DNA methylation-based therapeutic drugs for vascular aging-related diseases.

Research advance of Nrf2 on atherosclerosis by regulating vascular smooth muscle cell.

Atherosclerosis is a common pathological change in cardiovascular disease. Vascular smooth muscle cell is the main source of plaque cell and extracellular matrix, and nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcription factor regulating the function of vascular smooth muscle cell. In the process of atherosclerosis, Nrf2 signaling pathway has the following regulatory effects on vascular smooth muscle cell: regulating the phenotype of vascular smooth muscle cell to change to the direction conducive to the alleviation of disease progression; inhibiting the proliferation and migration of vascular smooth muscle cell; mitigating the level of blood lipid; alleviating vascular smooth muscle cell calcification, aging and apoptosis process. This article reviews the specific mechanisms of Nrf2 regulating atherosclerosis, such as phenotypic transformation, proliferation and migration, lipid metabolism, calcification, aging and apoptosis in atherosclerosis, in order to provide a basis for understanding the molecular mechanism of atherosclerosis development and finding therapeutic targets.

ARTERIAL STIFFNESS PARAMETERS AS INDICATORS OF CORONARY ARTERY DISEASE IN YOUNG PATIENTS

Objective: To assess the state of the arterial bed in patients with CAD with varying degrees of coronary artery injuries (CA) and healthy peers. Design and method: The study included 92 patients with CAD (mean age 41.3 ± 8.2 years). Inclusion criteria: CAD verified by coronary angiography (CAG), ECG and/or biomarkers, hospitalization for unstable angina. After CAG, the patients were divided into 3 groups: the first - 30 people without hemodynamically significant stenoses (HSS1 < 50%) of CA, the second - 37 patients with HSS of 1 CA (HSS1 > 50%), the third group - 35 patients with HSS 2 or more CA (HSS2 > 50%). The control (C) group consisted of 28 healthy individuals. Regional arterial stiffness was assessed by volume sphygmography (Fukuda Denshi, Japan): R/L–PWV - PWV in elastic arteries, L-/CAVI-1 - cardio-ankle vascular index. Applanation tonometry (AtCorMedical, Australia) was used to record carotid-femoral PWV (cfPWV) and indicators of central aortic pressure: systolic (SBPao), pulse (PPao). Results: The lowest R/L-PWV values were in control - 10.1 ± 1.9 m/s; in patients with CAD, an increase in R/L-PWV was revealed in the HSS1 < 50% group - 11.9 ± 1.5 m/s and in the group HSS1 > 50% - 13.9 ± 0.9 m/s. The highest values were found in the group HSS2 > 50% - 13.9 (9.6;14.7) m/s (p < 0.05). The L-/CAVI-1 index in control was 6.4 (5.6;7.3), in group 1 - 7.2 (6.2;8.4), in group 2 - 8.3 (6.7;9.4) in group 3 - 9.5 (7.1;10.4) (p < 0.05). According to the applanation tonometry, in healthy people HSS1 < 50%, HSS1 > 50%, and HSS2 > 50%, a comparable level of central BP was recorded: SBPao - 100.9 ± 8.1mmHg, 100.5 ± 9.7mmHg, 100.3 ± 8.4mmHg 101.3 ± 7.7mmHg, PPao - 26.8 ± 6.1mmHg, 27.0 ± 5.9mmHg, 29.0 ± 5.3mmHg, 28.7 ± 6.4mmHg, respectively (p > 0.05), which is probably due to the examination in pharmacotherapy. The smallest cfPWV values were recorded in control - 6.5 ± 0.9 m/s compared with group 1 - 7.4 (6.2;8.7) m/s, in the group 2 - 8.5 ± 1.1 m/s, group 3 - 9.6 ± 1.4 m/s (p < 0.05). Conclusions: In patients with CAD, a significant violation of the vascular stiffness parameters was diagnosed, more pronounced in people with stenosis of two or more CA. The study results confirm that the CAD in young adult is a clinical manifestation of the widespread process of early vascular aging.

Association between physical performance and incidence of end-stage renal disease in older adults: a national wide cohort study

BackgroundPhysical frailty has previously been associated with adverse clinical outcomes in patients with end-stage renal disease (ESRD). This study aimed to determine whether impaired physical performance at baseline is associated with the incidence of ESRD, using a nationwide database.MethodsThe timed up-and-go (TUG) test was used to assess physical frailty in 1,552,781 66-year-old individuals, using health examination database records from the Korean National Health Insurance Service. As a primary endpoint, incident ESRD was defined operationally using healthcare claims data from the Korean Health Insurance Review and Assessment Service.ResultsOur results showed that baseline kidney function was significantly worse in individuals with TUG results of > 10 s compared to individuals with an intact TUG performance (≤10 s). Kaplan-Meier analysis showed a stepwise dose-response relationship between baseline physical performance and the incidence rate of ESRD (log-rank test P-value of < 0.001). An increasing ESRD incidence rate trend with poor physical performance remained significant after adjusting for characteristics such as baseline glomerular filtration rate and proteinuria.ConclusionPoor baseline physical performance was associated with an increased risk of ESRD, suggesting possible interactions between systemic frailty and vascular aging processes.

Research progress on the interaction between circadian clock and early vascular aging.

Considerable researches implicate that the circadian clock regulates the responsive rhythms of organs and sets the orderly aging process of cells indirectly. It influences an array of diverse biological process including intestinal flora, peripheral inflammatory responses, and redox homeostasis. People with sleep disoders and other kinds of circadian disruptions are prone to have vascular aging earlier. Meanwhile, those people are always faced with chronic vascular inflammation. It has not been elucidated that the specific mechanism of the interaction between the circadian system and early vascular aging. To explore the biphasic relationship between vascular aging and the circadian system, we summarize what is linking circadian clock with early vascular aging through four major prospect: inflammatory process, oxidative stress response, intestinal flora, and cellular senescence. Meanwhile, we discuss the hypothesis that the deterioration of circadian rhythms may exacerbate the process of early vascular aging, leading to the cardiovascular diseases. It will help us to provide new ideas for understanding the process of vascular aging and exploring the possible ways to design personalized chronotherapies.

Telomere Length and Oxidative Stress in Patients with ST-Segment Elevation and Non-ST-Segment Elevation Myocardial Infarction.

The telomere length is shown to act as a biomarker, especially for biological aging and cardiovascular diseases, and it is also suggested that with this correlation, increased exposure to the oxidative stress accelerates the vascular aging process. Therefore, this study aims to understand the correlation between the plasma oxidative stress index (OSI) status and leukocyte telomere length (LTL) and cardiologic parameters between the ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) groups. One hundred one newly diagnosed patients with STEMI (n=55) and NSTEMI (n=46) were included in the study, along with 100 healthy controls who matched the patients in terms of age and gender. Plasma total antioxidant status (TAS), total oxidant status (TOS), and LTL were measured. When LTL, TAS, TOS, and OSI values were evaluated between the patient and control group, OSI (p=0.000) and LTL (p=0.05) values were statistically significant in the patient group compared to the control group. Evaluation was conducted to understand whether there is a difference between the STEMI and NSTEMI groups. The plasma OSI (p=0.007) and LTL (p=0.05) were found to be significantly lower in STEMI patients. However, LTL and OSI results were not statistically significant in NSTEMI patients. This is the first study evaluating telomere length and oxidative stress in STEMI and NSTEMI patients in Turkey. Our results support the existence of short telomere length in STEMI patients. Future studies on telomere length and oxidative stress will support the importance of our findings.

Blood Pressure Increase and Microvascular Dysfunction Accelerate Arterial Stiffening in Children: Modulation by Physical Activity.

BackgroundAtherosclerotic remodeling starts early in life and can accelerate in the presence of cardiovascular risk (CV) factors. Regular physical activity (PA) can mitigate development of large and small artery disease during lifespan. We aimed to investigate the association of changes in body mass index (BMI), blood pressure (BP), PA behavior and retinal microvascular diameters with large artery pulse wave velocity (PWV) in prepubertal children over 4 years.MethodsThe school-based prospective cohort study included 262 children initially aged 6–8 years, assessing the above CV risk factors and retinal vessels by standardized procedures at baseline (2014) and follow-up (2018). PWV was assessed by an oscillometric device at follow-up.ResultsChildren with increased systolic BP over 4 years showed higher PWV at follow-up (β [95% CI] 0.006 [0.002 to 0.011] mmHg per unit, P = 0.002). In contrast, increased vigorous PA corresponded to a lower PWV at follow-up (β [95% CI] −0.009 [−0.018 to <0−0.001] 10 min/day per unit, P = 0.047). Progression of retinal arteriolar narrowing and venular widening were linked to a higher PWV after 4 years (β [95% CI] −0.014 [−0.023 to −0.004] 0.01 changes per unit, P = 0.003).ConclusionIncrease in systolic BP and progression of microvascular dysfunction were associated with higher PWV after 4 years. Children with increasing levels of vigorous PA were found to have lower PWV at follow-up. Habitual vigorous PA has the potential to decelerate the process of early vascular aging in children and may thus help counteract CV disease development later in life.Clinical Trial RegistrationClinicalTrials.gov, Identifier: NCT03085498.

New Insight into the Mechanisms of Ginkgo Biloba Extract in Vascular Aging Prevention.

Aging-associated vascular dysfunction promotes cardiovascular diseases. Recently, Ginkgo biloba extract (GBE) has attracted considerable attention in the prevention of aged vasculature. This review discusses the pathophysiological alterations in aged vasculature and the underlying mechanisms of GBE in vascular aging suppression. Both arterial stiffening and endothelial dysfunction are critical aging-related vascular phenotypes that result in the progression of cardiovascular diseases in the general population. Consistent oxidative stress and inflammatory reaction lead to vascular dysfunction. GBE ameliorates aging-related vascular dysfunction, due to its antioxidant and anti-inflammatory properties. The main effects of GBE in aged vasculature might be associated with the longevity signaling pathways. GBE also attenuates the progression of vascular aging in diabetes mellitus via regulation of glucose and lipid metabolism. GBE plays an important role in the prevention of vascular aging process. It is a promising therapeutic approach to ameliorate aging-related vascular dysfunction and cardiovascular diseases.

Determinants of Brachial-Ankle Pulse Wave Velocity and Vascular Aging in Healthy Older Subjects.

BackgroundVascular aging is characterized by increasing arterial stiffness as measured by pulse wave velocity. The present study evaluated the factors influencing vascular aging in Chinese healthy older subjects.Material/MethodsDisease- and treatment-free aged (≥60 years) participants were recruited from 2014 to 2019. Cardiometabolic risk factors and brachial-ankle pulse wave velocity (baPWV) were assessed. We defined healthy vascular aging (HVA) as the lowest 10% and early vascular aging (EVA) as the highest 10% of the baPWV distribution, after adjustment for age and blood pressure (BP). We fitted linear and logistic regression models to assess the determinants.ResultsIn all, 794 subjects (mean age 66.5±6.8 years, 71.0% male) were recruited; the 10th and 90th percentiles of baPWV were 1278 cm/s and 1955 cm/s, respectively. Age, BP, heart rate, and triglycerides were all positively associated with baPWV, whereas male subjects and body mass index (BMI) were negatively associated with baPWV. The number of participants diagnosed with either HVA or EVA was 80. Logistic regression models showed that sex, BMI, heart rate, and triglycerides were associated with HVA and EVA after adjustment for age, BP, and other confounding factors.ConclusionsMale, high BMI, low heart rate, and low triglycerides are protective factors for vascular aging in the healthy aged population. Management of BMI, heart rate, triglycerides in a reasonable range may help to alleviate the vascular aging process.

Circulating anti-geronic factors from heterochonic parabionts promote vascular rejuvenation in aged mice: transcriptional footprint of mitochondrial protection, attenuation of oxidative stress, and rescue of endothelial function by young blood.

Aging-induced functional and phenotypic alterations of the vasculature (e.g., endothelial dysfunction, oxidative stress) have a central role in morbidity and mortality of older adults. It has become apparent in recent years that cell autonomous mechanisms alone are inadequate to explain all aspects of vascular aging. The present study was designed to test the hypothesis that age-related changes in circulating anti-geronic factors contribute to the regulation of vascular aging processes in a non-cell autonomous manner. To test this hypothesis, through heterochronic parabiosis we determined the extent, if any, to which endothelial function, vascular production of ROS, and shifts in the vascular transcriptome (RNA-seq) are modulated by the systemic environment. We found that in aortas isolated from isochronic parabiont aged (20-month-old) C57BL/6 mice [A-(A); parabiosis for 8weeks] acetylcholine-induced endothelium-dependent relaxation was impaired and ROS production (dihydroethidium fluorescence) was increased as compared with those in aortas from young isochronic parabiont (6-month-old) mice [Y-(Y)]. The presence of young blood derived from young parabionts significantly improved endothelium-dependent vasorelaxation and attenuated ROS production in vessels of heterochronic parabiont aged [A-(Y)] mice. In aortas derived from heterochronic parabiont young [Y-(A)] mice, acetylcholine-induced relaxation and ROS production were comparable with those in aortas derived from Y-(Y) mice. Using RNA-seq we assessed transcriptomic changes in the aortic arch associated with aging and heterochronic parabiosis. We identified 347 differentially expressed genes in A-(A) animals compared with Y-(Y) controls. We have identified 212 discordant genes, whose expression levels differed in the aged phenotype, but have shifted back toward the young phenotype by the presence of young blood in aged A-(Y) animals. Pathway analysis shows that vascular protective effects mediated by young blood-regulated genes include mitochondrial rejuvenation. In conclusion, a relatively short-term exposure to young blood can rescue vascular aging phenotypes, including attenuation of oxidative stress, mitochondrial rejuvenation, and improved endothelial function. Our findings provide additional evidence supporting the significant plasticity of vascular aging and evidence for the existence of anti-geronic factors capable of exerting rejuvenating effects on the aging vasculature.

Early vascular ageing in chronic kidney disease: impact of inflammation, vitamin K, senescence and genomic damage.

Chronic kidney disease (CKD) is a clinical model of premature ageing characterized by cardiovascular disease, persistent uraemic inflammation, osteoporosis muscle wasting and frailty. The accelerated early vascular ageing (EVA) process mediated by medial vascular calcification (VC) is a hallmark of senescence as well as a strong predictor of cardiovascular morbidity and mortality in the CKD population. Current clinical therapeutic strategies and novel treatments for VC have not yet been proven to prevent or reverse VC progression in patients with CKD. Knowledge of the fundamental mechanism underlying EVA is urgently needed to identify and develop novel and efficient therapeutic targets for VC and EVA. An accumulating body of evidence indicates that deoxyribonucleic acid (DNA) damage–induced cellular senescence and ‘inflammaging’ may largely contribute to such pathological conditions characterized by accelerated EVA. Growing evidence shows that nuclear factor erythroid 2–related factor 2 (NRF2) signalling and vitamin K play a crucial role in counteracting oxidative stress, DNA damage, senescence and inflammaging, whereby NRF2 activation and vitamin K supplementation may provide a novel treatment target for EVA. In this review we discuss the link between senescence and EVA in the context of CKD, with a focus on the role of NRF2 and vitamin K in DNA damage signalling, senescence and inflammaging.

Trajectories of Age-Related Arterial Stiffness in Chinese Men and Women

BackgroundArterial stiffening is central in the vascular aging process. Traditionally, vascular research has focused on atherosclerotic vascular disease, whereas arterial stiffness has not attracted similar attention. ObjectiveSThe purpose of this study was to assess lifetime trajectories of arterial stiffening in Chinese populations facing a high burden of cardiovascular disease, with a particular focus on age–sex interactions and potential determinants. MethodsThis large-scale observational study comprised 2 independent cross-sectional population samples and 1 prospective cohort totaling 80,415 healthy subjects with brachial-ankle pulse wave velocity (baPWV) measurements available. Associations with potential risk conditions were analyzed using linear regression, linear random intercepts mixed models, and L1-regularized linear models. ResultsThe dynamics of age-dependent arterial stiffening differed in sexes, with stiffer vessel observed in men from adolescence to age 58 years and in women thereafter. The steeper increase in baPWV in women after menopause is partly explained by the fact that vascular risk factors are more strongly associated with arterial stiffness in women than in men. Age and systolic blood pressures were the strongest determinants of baPWV, whereas other vascular and metabolic risk factors, except low-density lipoprotein cholesterol, showed consistent associations of moderate strength. ConclusionsThe significant age–sex interaction in arterial stiffening provides an important clue of explanation for the heightened cardiovascular disease risk in postmenopausal women. Detailed knowledge on lifetime trajectories of arterial stiffening, and its potential risk factors is a prerequisite for the development of new prevention strategies counteracting vascular aging.

EFFECT OF THERAPY WITH A FIXED COMBINATION OF PERINDOPRIL AND AMLODIPINE ON VASCULAR AGE AND 5-YEAR RISK OF CARDIOVASCULAR COMPLICATIONS IN PATIENTS WITH ARTERIAL HYPERTENSION AND MILLITUS DIABETES TYPE 2

In recent years, the concept of cardiovascular risk factors, one of which is the process of vascular aging, has been of great interest. 30 patients with stage 2-3 of arterial hypertension and type 2 diabetes mellitus aged 45 to 65 years were included, including 23 women and 7 men. Patients after the washout period a fixed combination of perindopril with amlodipine (the original drug Prestans, AO Servier) in the form of tablets (perindopril arginine / amlodipine bezilat) were prescribed for 12 weeks, 1 time per day. Vascular age and 5-year risk of developing cardiovascular complications were calculated on the calculator app for smartphones ADVANTAGE AGE (Les laboratories Servier version 2, 2015). After 12-week therapy with a fixed combination of perindopril and amlodipine, the achievement of target blood pressure values was noted in 100 % of patients. The average passport age of the patients included in the study was (61,9 ± 4,4) [45; 65] years. In assessment vascular age, there was a statistically significant initial increase in vascular age above the passport age - (69,3 ± 8,5) [55; 89] years. 46,7 % of patients have an average risk of developing cardiovascular complications and 53,3 % of patients have a high risk of cardiovascular accidents. After 12 weeks of therapy with arginine perindopril and amlodipine bezilate, there was a significant decrease of vascular age to 63,1 ± 5,6 [51; 73] years, a decrease in the percentage of patients with high risk of cardiovascular complications to 23,4 % (p &lt; 0,05), due to patients with average risk (53,3 %, at p &lt; 0,05), and the appearance of patients (3,3 %) with a low risk of cardiovascular accidents within 5 years. In patients with arterial hypertension and diabetes millitus type 2, vascular age significantly increases in comparison with the passport age. The use of a fixed combination of perindopril arginine / amlodipine bezilate for 12 weeks in this category of patients significantly reduces the vascular age of patients and reduces the frequency of detection of patients with high and medium risk of cardiovascular accidents.

The Correlation between p53 Serum Levels and Vascular Age was Measured by Carotid Intima Media Thickness (CIMT) in Patients with Moderate Cardiovascular Risk Factors

Protein p53 has an important role in atherosclerosis plaque as part of senescence cell vascular. Increased vascular aging process is characterized by several parameters, one of which is an increase in carotid intima media thickness (CIMT). CIMT is one of the non-invasive methods that can determine vascular age, which is a safe, fast and inexpensive method of assessing atherosclerosis. This study was a correlational study conducted at cardiovascular outpatient clinic from August until November 2015. Serum p53 levels were measured by human p53 ELISA kit. CIMT is measured by B-mode ultrasound. The CIMT value was based on the normogram of the Atheosclerosis Risk in Communities Study. Spearman rank test was used to analyze the relationship between serum p53 and vascular age. There were 19 men and 19 women in the subject of this study. The average vascular age is 54.34 + 8.5 years. Serum p53 levels were positively correlated with vascular age in the subject group of this study (p <0.001; r = 0.58). There is a positive, strong and significant correlation between serum p53 and vascular age levels determined by CIMT in patients with moderate cardiovascular risk factors.

Genetic risk factors for vascular aging: molecular mechanisms, polymorphism of candidate genes and gene networks

Age is considered an independent and primary risk factor in the development of cardiovascular disease. Aging of vascular cells induces complex changes in the structure and functions of the vasculature. The article discusses a number of molecular genetic mechanisms involved in the pathogenesis of vascular aging: cell and mitochondrial dysfunction, endothelial dysfunction, depletion of the progenitor cell pool, shortening and damage to telomeres, chronic inflammation, oxidative stress, and dysregulation of vascular tone. There is more and more evidence of cross-involvement in the vascular aging processes of candidate genes (such as ACE, SIRT1, TERC, FOXO1, FOXO3, APOE, NOS3) associated with life expectancy and cardiovascular diseases. For 26 genes involved in the presented molecular mechanisms of vascular aging, sites of functional polymorphisms are given. Understanding the main pathophysiological changes caused by vascular aging makes it possible to choose a preventive strategy. Modern approaches for better predicting of genetic risk are discussed in conclusion using the example of visualization of vascular aging genes network.

P866Early vascular ageing and acute coronary syndromes in young patients

Abstract Purpose To evaluate the prevalence of atherosclerotic coronary lesions in young patients from a very high CV risk country, presented with a first ACS episode and to analyse the association between arterial stiffness, arterial age and the severity of CAD. Methods Sixty consecutive patients with age ≤45 years (mean age 41,25±3.99 years; range 22–45 years; 81.7% males) admitted in our department for a first ACS between January 2016 and January 2018 and underwent coronary angiography for evaluation of CAD were enrolled in the study after signing a written informed consent (ACS group) and compared with 60 healthy subjects, age and sex-matched, randomly selected from the SEPHAR III national representative survey's data base. Arterial stiffness parameters and arterial age were measured with an oscillometric device (Arteriograph). Association between arterial age and arterial stiffness and the severity of CAD was assessed by bivariate correlation analysis with adjustments for major confounders. Results The main pathogenic mechanism of ACS was represented by the coronarian atherosclerotic lesions (46 cases, representing 76,7%, p&lt;0,001) and the most frequent clinical form was the ST-segment elevation myocardial infarction (53 cases, representing 88,3%, p&lt;0,001). Of all those 46 patients from the SCA that have atherosclerotic lesions, most had univascular disease (univascular – 25 cases, 54.3% vs. bivascular: 14 cases, 30,4% vs. trivascular: 7 cases, 15.2%, p=0.005). ACS group had significantly higher PWVao values than CONTROL group, on average of 2, 87m/s [9,49±1,92 m/s vs. 6,62±1,12/s, p&lt;0.0001; 95% CI = (−3,43m/s; −2,29m/s)]. Arterial age of ACS patients was significantly higher than their own biological age, on average with 5.78 years [mean arterial age 47.03 vs. biological age: 41.25; p&lt;0.0001; 95% CI = (3.91ani; 7.66ani)] while arterial age and biological age were similar in CONTROL group [mean arterial age 40,53 ani vs. mean biological age: 39,63 ani; p=0,207; 95% CI = (−0,73ani; 3,29ani)]. In ACS group, while among patients with normal coronaries, the arterial and biological age were statistically similar (43.25 years vs. 41.53 years; p=0.500), in patients with atherosclerotic lesions (uni-, bi or tri vascular), arterial age was significantly higher compared to biological age, on average with 5.7 years, 5.7 years and 7.5 years respectively. Also, in STEMI group, the severity of CAD was correlated with both PWVao values [rs=0,521 rs2=0.271; p&lt;0,0001] and arterial age [rs=0,512 rs2=0.262; p=0.035]. Conclusions The results of our study shows that young ACS patients experience an early vascular ageing process reflected by an increased arterial stiffness and significantly higher vascular age compared with normal healthy age and sex-matched controls, leading to an early onset of CAD. Acknowledgement/Funding This work was supported by CREDO Project - ID: 49182, financed through the SOP IEC -A2-0.2.2.1-2013-1 cofinanced by the ERDF.

Inflammation and Vascular Ageing: From Telomeres to Novel Emerging Mechanisms.

Cardiovascular disease (CVD) remains the leading cause of morbility and mortality worldwide. The identification of common cardiovascular risk factors has led to the development of effective treatments that enabled a significant reduction of the global cardiovascular disease burden. However, a significant proportion of cardiovascular risk remains unexplained by these risk factors leaving many individuals at risk of cardiovascular events despite good control of the risk factors. Recent randomized clinical trials and Mendelian randomization studies have suggested that inflammation explains a significant proportion of the residual cardiovascular risk in subjects with good control of risk factors. An accelerated process of vascular ageing is increasingly recognized as a potential mechanism by which inflammation might increase the risk of CVD. In turn, cellular ageing represents an important source of inflammation within the vascular wall, potentially creating a vicious cycle that might promote progression of atherosclerosis, independently from the individual cardiovascular risk factor burden. In this review, we summarise current evidence suggesting a role for biological ageing in CVD and how inflammation might act as a key mediator of this association.