Association of the Single Nucleotide Polymorphisms in the Renin-Angiotensin-Aldosterone System with Hypertension in the Uzbek Population.

OBJECTIVE: This research aims to identify the association between the nine polymorphic variants (rs4961, rs699, rs4762, rs5186, rs1403543, rs1799998, rs5443, rs2070744, rs1799983) and the occurrence of hypertension and its clinical manifestations in the Uzbek population. METHODS: The study included 227 individuals, comprising 179 patients with hypertension and 48 controls. Clinical parameters such as age, weight, blood glucose, triglycerides, total cholesterol, low-density lipoprotein and high-density lipoprotein, blood urea nitrogen, creatinine, pulse wave velocity, left ventricular mass, and microalbuminuria levels were identified. We assessed the distribution of allele frequencies of these polymorphic variants in the Uzbek population to establish their association with cardiovascular diseases and their clinical manifestations. RESULTS: Genetic analysis of the polymorphic variants demonstrated a significant association of the AGT 521 C>T variant with arterial hypertension [P ≤ 0.01; Odds Ratio (OR) = 2.91]. The NOS3 -786 T>C variant correlated with left ventricular hypertrophy (P ≤ 0.05; OR = 0.35) and increased pulse wave velocity (P ≤ 0.01; OR = 0.21). The correlations of the AGTR2 1675 G>A variant with left ventricular hypertrophy (P ≤ 0.01; OR = 1.59) and increased pulse wave velocity (P ≤ 0.01; OR = 0.33) were identified. The AGT 704 T>C variant showed a significant association with increased pulse wave velocity (P ≤ 0.05; OR = 2.73). CONCLUSION: Four of the nine studied polymorphic variants were associated with clinical manifestations of hypertension in the Uzbek population. These variants can be used as genetic biomarkers to identify the risks of developing cardiovascular diseases and hypertension in the Uzbek population.

Association between Gene Polymorphisms and SNP-SNP Interactions of the Matrix Metalloproteinase 2 Signaling Pathway and the Risk of Vascular Senescence.

Objective: This study aimed to explore the association of single nucleotide polymorphisms (SNP) in the matrix metalloproteinase 2 (MMP-2) signaling pathway and the risk of vascular senescence (VS). Methods: In this cross-sectional study, between May and November 2022, peripheral venous blood of 151 VS patients (case group) and 233 volunteers (control group) were collected. Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway, assessed through carotid-femoral pulse wave velocity (cfPWV), and analyzed using multivariate logistic regression. The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction (MDR) and generalized multifactor dimensionality regression (GMDR) modeling. Results: Within the multivariate logistic regression models, four SNPs were screened to have significant associations with VS: chemokine (C-C motif) ligand 2 (CCL2) rs4586, MMP2 rs14070, MMP2 rs7201, and MMP2 rs1053605. Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype, and those of the T/T genotype had a 19.375-fold increased risk. CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions. Conclusion: CCL2 rs4586, MMP-2 rs14070, MMP-2 rs7201, and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.

Correlation between estimated pulse wave velocity values from two equations in healthy and under cardiovascular risk populations.

INTRODUCTION: Equations can calculate pulse wave velocity (ePWV) from blood pressure values (BP) and age. The ePWV predicts cardiovascular events beyond carotid-femoral PWV. We aimed to evaluate the correlation between four different equations to calculate ePWV. METHODS: The ePWV was estimated utilizing mean BP (MBP) from office BP (MBPOBP) or 24-hour ambulatory BP (MBP24-hBP). We separated the whole sample into two groups: individuals with risk factors and healthy individuals. The e-PWV was calculated as follows: [Formula: see text] [Formula: see text] We calculated the concordance correlation coefficient (Pc) between e1-PWVOBP vs e2-PWVOBP, e1-PWV24-hBP vs e2-PWV24-hBP, and mean values of e1-PWVOBP, e2-PWVOBP, e1-PWV24-hBP and e2-PWV24-hBP. The multilevel regression model determined how much the ePWVs are influenced by age and MBP values. RESULTS: We analyzed data from 1541 individuals; 1374 ones with risk factors and 167 healthy ones. The values are presented for the entire sample, for risk-factor patients and for healthy individuals respectively. The correlation between e1-PWVOBP with e2-PWVOBP and e1-PWV24-hBP with e2-PWV24-hBP was almost perfect. The Pc for e1-PWVOBP vs e2-PWVOBP was 0.996 (0.995-0.996), 0.996 (0.995-0.996), and 0.994 (0.992-0.995); furthermore, it was 0.994 (0.993-0.995), 0.994 (0.994-0.995), 0.987 (0.983-0.990) to the e1-PWV24-hBP vs e2-PWV24-hBP. There were no significant differences between mean values (m/s) for e1-PWVOBP vs e2-PWVOBP 8.98±1.9 vs 8.97±1.8; p = 0.88, 9.14±1.8 vs 9.13±1.8; p = 0.88, and 7.57±1.3 vs 7.65±1.3; p = 0.5; mean values are also similar for e1-PWV24-hBP vs e2-PWV24-hBP, 8.36±1.7 vs 8.46±1.6; p = 0.09, 8.50±1.7 vs 8.58±1.7; p = 0.21 and 7.26±1.3 vs 7.39±1.2; p = 0.34. The multiple linear regression showed that age, MBP, and age2 predicted more than 99.5% of all four e-PWV. CONCLUSION: Our data presents a nearly perfect correlation between the values of two equations to calculate the estimated PWV, whether utilizing office or ambulatory blood pressure.

Maternal Seafood Consumption during Pregnancy and Cardiovascular Health of Children at 11 Years of Age.

Nutrition is critical during pregnancy for the healthy growth of the developing infant, who is fully dependent on maternal dietary omega-3 supply for development. Fatty fish, a main dietary source of omega-3, is associated with decreased cardiovascular risk in adults. We conducted a longitudinal study based on a mother-offspring cohort as part of the project Infancia y Medio Ambiente (INMA) in order to assess whether fish intake during pregnancy relates to cardiovascular health in children. A total of 657 women were included and followed throughout pregnancy until birth, and their children were enrolled at birth and followed up until age 11-12. A semi-quantitative food frequency questionnaire was used to assess the daily intake of foods during the 1st and 3rd trimesters of pregnancy. Cardiovascular assessments included arterial stiffness (assessed by carotid-femoral pulse wave velocity [PWV]) and retinal microcirculation (photographic assessment of central retinal arteriolar and venular equivalent [CRAE and CRVE]). The association between maternal fish consumption and cardiovascular outcomes of offspring at 11 years of age was evaluated using multivariable linear regression models. There were no statistically significant differences in any cardiovascular endpoint in children whose mothers had a higher fish consumption during pregnancy compared to those with a lower fish consumption. We found a slightly higher PWV (ß = 0.1, 95% CI = 0.0; 0.2, p for trend = 0.047) in children whose mothers had a higher consumption of canned tuna during the 1st trimester of pregnancy. Fish intake during pregnancy was found to be unrelated to the offspring's cardiovascular health at 11 years of age. The beneficial cardiovascular effects of fish consumption during pregnancy on the offspring are still inconclusive.

Higher Arterial Stiffness Predicts Chronic Kidney Disease in Adults: The ELSA-Brasil Cohort Study. / Maior Rigidez Arterial Prediz Doença Renal Crônica no Estudo de Coorte ELSA-Brasil.

BACKGROUND: Central Illustration : Higher Arterial Stiffness Predicts Chronic Kidney Disease in Adults: The ELSA-Brasil Cohort Study. BACKGROUND: Arterial stiffening can directly affect the kidneys, which are passively perfused by a high flow. However, whether the relation between arterial stiffness and renal function depends on diabetes and hypertension conditions, is a matter of debate. OBJECTIVE: To investigate the relationship between arterial stiffening by carotid-to-femoral pulse wave velocity (cfPWV) and chronic kidney disease (CKD) incidence in individuals and verify whether this association is present in individuals without hypertension and diabetes. METHODS: A longitudinal study of 11,647 participants of the ELSA-Brasil followed up for four years (2008/10-2012/14). Baseline cfPWV was grouped per quartile, according to sex-specific cut-offs. Presence of CKD was ascertained by glomerular filtration rate (eGFR-CKD-EPI) < 60 ml/min/1.73 m2 and/or albumin-to-creatinine ratio ≥ 30 mg/g. Logistic regression models were run for the whole cohort and a subsample free from hypertension and diabetes at baseline, after adjustment for age, sex, race, schooling, smoking, cholesterol/HDL ratio, body mass index, diabetes, use of antihypertensive, systolic blood pressure, heart rate, and cardiovascular disease. Statistical significance was set at 5%. RESULTS: The chance of CKD was 42% (CI 95%: 1.05;1.92) greater among individuals in the upper quartile of cfPWV. Among normotensive, non-diabetic participants, individuals in the 2nd, 3rd, and 4th quartiles of cfPWV presented greater chances of developing CKD, as compared to those in the lower quartile, and the magnitude of this association was the greatest for those in the upper quartile (OR: 1.81 CI 95%: 1.14;2.86). CONCLUSION: Higher cfPWV increased the chances of CKD and suggests that this effect is even greater in individuals without diabetes and hypertension.

Short-duration dynamic power training with elastic bands combined with endurance training: a promising approach to hypertension management in older adults.

Previous studies have investigated the effects of different combined training programs involving traditional resistance training and aerobic exercise on hemodynamic parameters and arterial stiffness in older adults. However, little is known about the impact of power training combined with endurance training on these variables in hypertensive older adults. Therefore, this study aimed to investigate the effects of dynamic power training with elastic bands combined with endurance training on arterial stiffness and hemodynamic parameters in hypertensive older adults. Twenty-six participants were randomly assigned to the control group (CG; n = 13) and the intervention group (n = 13). IG participants performed power training with elastic bands combined with endurance training twice a week for 8 weeks. Pulse pressure, central pulse pressure, pulse wave velocity, SBP, DBP, central SBP, and central DBP were assessed before and after 8 weeks using the triple pulse wave velocity method. Pulse pressure, central pulse pressure, pulse wave velocity, SBP, DBP, central SBP, and central DBP significantly improved after 8 weeks of intervention (P < 0.05). These findings indicate that power training with elastic bands combined with endurance training reduces arterial stiffness and significantly improves hemodynamic parameters in older adults diagnosed with grade 1 hypertension. In addition, underscores the potential of this approach as a promising strategy for the management of hypertension in older adults.

Screening for Peripheral Vascular Stiffness in Lipedema Patients by Automatic Electrocardiogram-Based Oscillometric Detection.

Body mass index (BMI) is seen as a predictor of cardiovascular disease (CVD) in lipedema patients. A valid predictor of CVD is increased aortic stiffness (IAS), and previous research described IAS in lipedema. However, it is not known if this applies to all patients. In this cross-sectional single-center cohort study, peripheral pulse wave velocity (PWV) as a non-invasive indicator of aortic stiffness was measured in 41 patients with lipedema, irrespective of stage and without pre-existing cardiovascular conditions or a history of smoking and a maximum body mass index (BMI) of 35 kg/m2. Automatically electrocardiogram-triggered oscillometric sensor technology by the Gesenius-Keller method was used. Regardless of the stage of lipedema disease, there was no significant difference in PWV compared to published standard values adjusted to age and blood pressure. BMI alone is not a predictor of cardiovascular risk in lipedema patients. Measuring other anthropometric factors, such as the waist-hip ratio or waist-height ratio, should be included, and the existing cardiovascular risk factors, comorbidities, and adipose tissue distribution for accurate risk stratification should be taken into account. Automated sensor technology recording the PWV represents a valid and reliable method for health monitoring and early detection of cardiovascular risks.

Mean platelet volume (MPV) as new marker of diabetic macrovascular complications in patients with different glucose homeostasis : Platelets in cardiovascular risk.

BACKGROUND: Platelets play an important role in the development of cardiovascular disease (CVD). Mean platelet volume (MPV) is considered as biological marker of platelets activity and function. The aim of the present study was to evaluate MPV values and its possible correlation with arterial stiffness and subclinical myocardial damage, in normal glucose tolerance patients (NGT), in newly diagnosed type 2 diabetic (T2DM) patients and in individuals with pre-diabetes. METHODS: We enrolled 400 newly diagnosed hypertensive patients. All patients underwent an Oral Glucose Tolerance test (OGTT). Arterial stiffness (AS) was evaluated with the measurement of carotid-femoral pulse wave velocity (PWV), augmentation pressure (AP) and augmentation index (AI). Echocardiographic recordings were performed using an E-95 Pro ultrasound system. RESULTS: Among groups there was an increase in fasting plasma glucose (FPG) (p < 0.0001), fasting plasma insulin (FPI) (p < 0.0001), high sensitivity c reactive protein (hs-CRP) levels (p < 0.0001) and a decrease in renal function as demonstrated by e-GFR values (p < 0.0001). From the NGT group to the T2DM group there was a rise in MPV value (p < 0.0001). Moreover, in the evaluation of arterial stiffness and subclinical myocardial damage, MPV showed a positive correlation with these parameters. CONCLUSIONS: In the present study we highlighted that MPV is significantly increased, not only in newly diagnosed T2DM patients, but also in early stage of diabetes, indicating that subjects with pre-diabetes present increased platelets reactivity. Moreover, our results suggest that MPV is associated with increased arterial stiffness and subclinical myocardial damage, indicating MPV as new marker of CV risk.

An Atherosclerosis Indicator Hyaluronic Acid: Can Plasma Hyaluronic Acid Be Useful in Diagnosing Alzheimer's Disease?

BACKGROUND: The aim is to compare the plasma levels of hyaluronic acid (HA) which is closely related to inflam-mation and vascular changes and arterial stiffness (AS) related values in patients with Alzheimer's disease (AD), amnestic type mild cognitive impairment (aMCI), and normal cognitive functions (NCF). METHODS: Ninety participants were categorized into three groups, patients with AD, MCI, and NCF. Arterial stiffness measurement in the nephrology outpatient clinic, and storage and analysis of plasma samples in the biochemistry laboratory. RESULTS: Of the 90 patients, 32 had NCF, 32 had aMCI, and 26 had AD. Between groups, there was no difference in HA, pulse wave velocity, and augmentation index. The HA level had no statistically significant correlation with any of the other variables. CONCLUSIONS: Plasma HA levels will not be useful in the diagnosis of AD. More comprehensive studies with larger number of patients are needed.

The Association of Total Meat Intake with Cardio-Metabolic Disease Risk Factors and Measures of Sub-Clinical Atherosclerosis in an Urbanising Community of Southern India: A Cross-Sectional Analysis for the APCAPS Cohort.

AIM: Meat is commonly consumed in India; however, in comparison to Western settings, it is eaten in relatively lower quantities and with minimal processing. The association between meat intake and cardio-metabolic diseases (CMDs) and their risk factors in India is currently uncertain. We examined whether meat intake is associated with risk factors for CMDs and the measures of subclinical atherosclerosis in urbanising villages in southern India. METHODS: We conducted a cross-sectional analysis of 6012 adults (52.3% male) participating in the Andhra Pradesh Children and Parents' Study (APCAPS), which is a large prospective, intergenerational cohort study in Southern India that began with the long-term follow-up of the Hyderabad Nutrition Trial (1987-1990). We used cross-sectional data from the third wave of data collection conducted in 2010-2012, where total meat intake was assessed using 100-item, semi-quantitative validated food frequency questionnaires (FFQ). The FFQs were validated using multiple weighed 24 h dietary recalls. The main predictor, 'total meat intake', was calculated as the sum of chicken, red meat, and fish consumption. The risk factors for CMDs [systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), waist circumference (WC), fasting glucose, total cholesterol, homeostasis model assessment insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, and C-reactive protein] and measures of subclinical atherosclerosis [Carotid Intima-Media Thickness, Pulse Wave Velocity, and Augmentation Index] were assessed using standardised clinical procedures. Stratified by gender, the association of meat intake with the risk factors of CMDs and measures of subclinical atherosclerosis was examined using linear multilevel models with random intercept at the household level. RESULTS: The mean (SD) age of the male (n = 3128) and female participants (n = 2828) was 34.09 years (15.55) and 34.27 years (12.73), respectively. The median (IQR) intake of meat was 17.79 g/day (8.90, 30.26) in males and 8.90 g/day (4.15, 18.82) in females. In males, a 10 g increase in total meat intake/1000 Kcal/day was positively associated with DBP, BMI, WC, total cholesterol, LDL-C, and triglycerides, whereas in females, a 10 g increase in total meat intake/1000 Kcal/day was positively associated with SBP, DBP, fasting glucose, HOMA-IR, total cholesterol, LDL-C, and triglycerides. There was no relationship between meat consumption and measures of subclinical atherosclerosis. CONCLUSIONS: Meat intake had a linear positive association with CMD risk factors among the relatively younger Indian population who were consuming meat at lower levels compared to their European counterparts.

Acute effects of low-intensity one-legged electrical muscle stimulation on arterial stiffness in experimental and control limbs.

The aim of this study was to examine the acute effects of low-intensity one-legged electrical muscle stimulation (EMS) for skeletal muscle on arterial stiffness in EMS and non-EMS legs. Eighteen healthy subjects received two different protocols (Control (CT) and Experimental (ET) trials) in random order on separate days. EMS was applied to the left lower limb at 4 Hz for 20 min at an intensity corresponding to an elevation in pulse rate of approximately 15 beats/min (10.9 ± 5.1% of heart rate reserve). Before and after the experiment, arterial stiffness parameters in the control right leg (CRL) and control left leg (CLL) in CT and non-EMS leg (NEL) and EMS leg (EL) in ET were assessed by pulse wave velocity (baPWV, faPWV) and cardio-ankle vascular index (CAVI). No significant changes in all parameters were observed in either leg in CT. Conversely, in ET, low-intensity, single-leg EMS significantly reduced CAVI, baPWV, and faPWV in the EL, but not in the NEL. Acute, low-intensity single-leg EMS reduces arterial stiffness only in the EL. These data support our idea that physical movement-related regional factors rather than systematic factors are important for inducing acute reductions in arterial stiffness.

The associations of depressive symptoms and perceived stress with arterial health in adolescents.

Cardiovascular and mental diseases are among the most important global health problems, but little is known on the associations between mental and arterial health in adolescents. Therefore, we investigated the associations of arterial health with depressive symptoms and perceived stress in adolescents. A total of 277 adolescents, 151 boys, 126 girls, aged 15-17 years participated in the study. Depressive symptoms were assessed using the Beck Depression Inventory and perceived stress by the Cohen Perceived Stress Scale. Arterial health was assessed by measures from carotid ultrasonography (carotid intima-media thickness, Young's Elastic Modulus, carotid artery distensibility, stiffness index), impedance cardiography (pulse wave velocity, cardio-ankle vascular index), and pulse contour analysis (reflection index, stiffness index). The data were analyzed using linear regression models adjusted for age and sex. Depressive symptoms or perceived stress were not associated with indices of arterial health in the whole study group (ß = -0.08 to 0.09, p > 0.05), in boys (ß = -0.13 to 0.10, p > 0.05) or in girls (standardized regression coefficient ß = -0.16 to 0.08, p > 0.05). We found no associations of depressive symptoms and perceived stress with arterial health in adolescents. These observations suggest that the association between mental and arterial health problems develop in later life.

Combined effects of sleep and objectively-measured daily physical activity on arterial stiffness in middle-aged and older adults.

Although sleep quality and physical activity (PA) may influence on arterial stiffness, the combined effects of these two factors on arterial stiffness remain unknown. A total of 103 healthy middle-aged and older men and women (aged 50-83 years) with no history of cardiovascular disease and depression were included in this study. Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV), brachial-ankle PWV (baPWV), and femoral-ankle PWV (faPWV). Poor sleepers were defined as those with a Pittsburgh Sleep Quality Index score of >5.5. Using an accelerometer for seven consecutive days, low levels of PA were defined as low moderate-to-vigorous-intensity PA (MVPA) <19.0 min/day and low step counts <7100 steps/day, respectively. Poor sleepers with low PA levels, as determined by MVPA and daily steps, showed higher cfPWV, but not faPWV or baPWV, in middle-aged and older adults. Furthermore, in the analysis of covariance (ANCOVA) analyses adjusted for age, obesity, dyslipidemia, and sedentary behavior, the cfPWV result remained significant. Our study revealed that the coexistence of poor sleep quality and decreased PA (low MVPA or daily steps) might increase central arterial stiffness in middle-aged and older adults. Therefore, adequate sleep (good and sufficient sleep quality) and regular PA, especially at appropriate levels of MVPA (i.e., at least of 7100 steps/day), should be encouraged to decrease central arterial stiffness in middle-aged and older adults.

Correlation between the cardiometabolic index and arteriosclerosis in patients with type 2 diabetes mellitus.

BACKGROUND: The cardiometabolic index (CMI) is a new metric derived from the triglyceride-glucose index and body mass index and is considered a potential marker for cardiovascular risk assessment. This study aimed to examine the correlation between the CMI and the presence and severity of arteriosclerosis in patients with type 2 diabetes mellitus (T2DM). METHODS: This study involved 2243 patients with T2DM. The CMI was derived by dividing the triglyceride level (mmol/L) by the high-density lipoprotein level (mmol/L) and then multiplying the quotient by the waist-to-height ratio. Multivariate logistic regression was used to analyze the correlations between the CMI and BMI blood biomarkers, blood pressure, and brachial-ankle pulse wave velocity (baPWV). RESULTS: Patients were categorized into three groups based on their CMI: Group C1 (CMI < 0.775; n = 750), Group C2 (CMI: 0.775-1.355; n = 743), and Group C3 (CMI > 1.355; n = 750). Increased BMI, fasting glucose, insulin (at 120 min), total cholesterol (TC), and baPWV values were observed in Groups C2 and C3, with statistically significant trends (all trends P < 0.05). The CMI was positively correlated with systolic blood pressure (r = 0.74, P < 0.001). Multivariate analysis revealed that an increased CMI contributed to a greater risk for arteriosclerosis (OR = 1.87, 95%CI: 1.66-2.10, P < 0.001). Compared to the C1 group, the C2 group and C3 group had a greater risk of developing arteriosclerosis, with ORs of 4.55 (95%CI: 3.57-5.81, P<0.001) and 5.56 (95%CI: 4.32-7.17, P<0.001), respectively. The association was notably stronger in patients with a BMI below 21.62 kg/m² than in those with a BMI of 21.62 kg/m² or higher (OR = 4.53 vs. OR = 1.59). CONCLUSIONS: These findings suggest that the CMI is a relevant and independent marker of arteriosclerosis in patients with T2DM and may be useful in the risk stratification and management of these patients.

Exploring the Influence of Insulin Resistance on Arterial Stiffness in Healthy Adults: From the Metabolic and Cardiovascular Health Insights of the EVasCu Study.

Previous evidence associates insulin resistance with arterial stiffness in various pathologies, yet limited reports exist in healthy adults. Therefore, this study aims to estimate the association between insulin resistance and arterial stiffness in healthy adults. The cross-sectional EVasCu study enrolled 390 participants (42.05 ± 13.15 years). ANCOVAs, unadjusted (model 1) and adjusted (model 2), explored the association between arterial stiffness markers (aortic Pulse Wave Velocity [aPWV], Augmentation Index [AIx@75] and Cardio-Ankle Vascular Index [CAVI]), and insulin resistance markers (Homeostasis Model Assessment of Insulin Resistance [HOMA-IR], Quantitative Insulin Sensitivity Check Index [QUICKI] and Triglycerides-Glucose [TyG]). In model 1, all insulin resistance markers were associated with aPWV, HOMA-IR and QUICKI were associated with AIx@75, and the TyG index was associated with CAVI. In model 2, HOMA-IR and QUICKI increased aPWV by 0.179 and 0.156 m/s (p = 0.001 and p = 0.011), and AIx@75 by 4.17 and 5.39% (p = 0.009 and p = 0.003). The EVasCu study offers valuable insights into the relationship between insulin resistance and arterial stiffness in healthy adults, providing a deeper understanding of metabolic and cardiovascular health. By examining this influence, we embark on an intriguing exploration of how these factors interplay in the human body.

Cardiovascular hardware simulator and artificial aorta-generated central blood pressure waveform database according to various vascular ages for cardiovascular health monitoring applications.

This study presents a database of central blood pressure waveforms according to cardiovascular health conditions, to supplement the lack of clinical data in cardiovascular health research, constructed by a cardiovascular simulator. Blood pressure (BP) is the most frequently measured biomarker, and in addition to systolic and diastolic pressure, its waveform represents the various conditions of cardiovascular health. A BP waveform is formed by overlapping the forward and reflected waves, which are affected by the pulse wave velocity (PWV). The increase in vascular stiffness with aging increases PWV, and the PWV-age distribution curve is called vascular age. For cardiovascular health research, extensive data of central BP waveform is essential, but the clinical data published so far are insufficient and imbalanced in quantity and quality. This study reproduces the central BP waveform using a cardiovascular hardware simulator and artificial aortas, which mimic the physiological structure and properties of the human. The simulator can adjust cardiovascular health conditions to the same level as humans, such as heart rate of 40-100 BPM, stroke volume of 40-100 mL, and peripheral resistance of 12 steps. Also, 6 artificial aortas with vascular ages in the 20-70 were fabricated to reproduce the increase in vascular stiffness due to aging. Vascular age calculated from measured stiffness of artificial aorta and central BP waveform showed an error of less than 3 years from the clinical value. Through this, a total of 636 waveforms were created to construct a central BP waveform database according to controlled various cardiovascular health conditions.

Plasma metabolomics identifies S-adenosylmethionine as a biomarker and potential therapeutic target for vascular aging in older adult males.

Brachial-ankle pulse wave velocity (baPWV) is a noninvasive index of vascular aging. However, the metabolic profile underlying vascular aging has not yet been fully elucidated. The current study aimed to identify circulating markers of vascular aging as assessed by baPWV and to elucidate its mechanism from a metabolomic perspective in older adults. A total of 60 and 61 Chinese male participants aged ≥80 years were recruited to the metabolome and validation cohorts, respectively. The baPWV of participants was measured using an automatic waveform analyzer. Plasma metabolic profile was investigated using ultra-performance liquid chromatography coupled with triple quadrupole linear ion trap tandem mass spectrometry. Orthogonal partial least squares (OPLS) regression modeling established the association between metabolic profile and baPWV to determine important metabolites predictive of vascular aging. Additionally, an enzyme-linked immunosorbent assay was employed to validate the metabolites in plasma and culture media of vascular smooth muscle cells in vitro. OPLS modeling identified 14 and 22 metabolites inversely and positively associated with baPWV, respectively. These 36 biomarkers were significantly enriched in seven metabolite sets, especially in cysteine and methionine metabolism (p <0.05). Notably, among metabolites involved in cysteine and methionine metabolism, S-adenosylmethionine (SAM) level was inversely related to baPWV, with a significant correlation coefficient in the OPLS model (p <0.05). Furthermore, the relationship between SAM and vascular aging was reconfirmed in an independent cohort and at the cellular level in vitro. SAM was independently associated with baPWV after adjustments for clinical covariates (ß = -0.448, p <0.001) in the validation cohort. In summary, plasma metabolomics identified an inverse correlation between SAM and baPWV in older males. SAM has the potential to be a novel biomarker and therapeutic target for vascular aging.

Effects of Liraglutide, Empagliflozin and Their Combination on Left Atrial Strain and Arterial Function.

Background and Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are cardioprotective drugs. We investigated their effects on left atrial function, a major determinant of cardiac diastolic dysfunction in type 2 diabetes mellitus. We also explored the association of changes in arterial stiffness with those of the LA strain after treatment. Materials and Methods: A total of 200 patients (59.5 ± 9.1 year old, 151 male) with type 2 diabetes mellitus treated with metformin were randomized to insulin (n = 50 served as controls), liraglutide (n = 50), empagliflozin (n = 50) or their combination (liraglutide + empagliflozin) (n = 50). We measured at baseline and 6 months post-treatment: (a) left atrial and global left ventricular longitudinal strain by speckle tracking echocardiography; (b) pulse wave velocity (PWV) and central systolic blood pressure. Results: At baseline, there was a correlation of the LA reservoir strain with PWV (r = -0.209, p = 0.008), central SBP (r = -0.151, p = 0.030), EF (r = 0.214, p = 0.004) and GLS (r = -0.279, p = 0.009). The LA reservoir change 6 months post-treatment was correlated with the PWV change in all groups (r = -0.242, p = 0.028). The LA reservoir change 6 months post-treatment was correlated with the GLS change in all groups (r = -0.322, p = 0.004). Six months after intervention, patients treated with liraglutide, empagliflozin and their combination improved the left atrial reservoir strain (GLP1RA 30.7 ± 9.3 vs. 33.9 ± 9.7%, p = 0.011, SGLT2i 30 ± 8.3 vs. 32.3 ± 7.3%, p = 0.04, GLP1&SGLT2i 29.1 ± 8.7 vs. 31.3 ± 8.2, p = 0.007) compared to those treated with insulin (33 ± 8.3% vs. 32.8 ± 7.4, p = 0.829). Also, patients treated with liraglutide and the combination liraglutide and empagliflozin had improved left atrial conduction strain (p < 0.05). Empagliflozin or the combination liraglutide and empagliflozin showed a greater decrease of PWV and central and brachial systolic blood pressure than insulin or GLP-1RA. (p < 0.05). Conclusions: Impaired aortic elastic properties are associated with a decreased LA strain in type 2 diabetics. Treatment with liraglutide, empagliflozin and their combination for 6 months showed a greater improvement of left atrial function compared to insulin treatment in parallel with the improvement of arterial and myocardial functions.

Arterial Stiffness May Predict Subsequent Cancer Therapy-Related Cardiac Dysfunction in Breast Cancer Patients.

Cancer therapy-related cardiac dysfunction (CTRCD) is still a serious problem. Existing risk scores are insufficient for risk classification, especially in low and medium-risk patients. This study aims to evaluate if arterial stiffness (AS) measurement, which is associated with most of the known risk factors, can be a useful parameter for predicting subsequent CTRCD in patients with breast cancer (BC). Patients with BC were included in the study. All patients' AS parameters such as pulse wave velocity (PWV), augmentation index (AIx), augmentation pressure (AP), and echocardiographic parameters were obtained before treatment. During treatment, echocardiographic follow-up with routine parameters and left ventricle global longitudinal strain (LVGLS) were measured. Patients were evaluated on whether CTRCD occurred or not. A total of 67 patients were analyzed. The mean age of the study population was 54.9 ± 11 years. Baseline characteristics were similar except for age. No CTRCD diagnosis was obtained according to left ventricle ejection fraction (LVEF) reduction, but 18 patients (26.8%) developed CTRCD regarding the decline in LVGLS. Left ventricle hypertrophy and diastolic dysfunction were more frequent in patients with CTRCD (p = 0.016 and p = 0.015, respectively). PWV, AIx, and AP as AS parameters were significantly higher in patients with CTRCD, but Alx@75 were not (p = 0.005, p = 0.034, p = 0.008, p = 0.077, respectively). A positive correlation between PWV and a decreased percent in LVGS (R = 0.607, p < 0.001) was observed. ROC curve analyses revealed an AUC of 0.747 (p = 0.02, 95% CI 0.632-0.832) for PWV. A PWV value of 9.2 m/s predicted CTRCD with 94% sensitivity and 73% specificity. AS measurement may be useful for predicting CTRCD in patients with low to medium-risk BC.

Thoracic aorta injury detected by 4D flow MRI predicts subsequent main adverse cardiovascular events in breast cancer patients receiving anthracyclines: A longitudinal study.

PURPOSE: To investigate longitudinal thoracic aorta injury using 3-dimensional phase-contrast magnetic resonance imaging (4D flow MRI) parameters and to evaluate their value for predicting the subsequent main adverse cardiovascular events (MACEs) in breast cancer patients receiving anthracyclines. METHODS: Between July 2020 and July 2021, eighty-eight female participants with breast cancer scheduled to receive anthracyclines with or without trastuzumab prospectively enrolled. Each subjects underwent 4D flow MRI at baseline, 3 and 6 months in relation to baseline. The diameter, peak velocity (Vpeak), wall shear stress (WSS), pulse wave velocity (PWV), energy loss (EL) and pressure gradient (PG) of thoracic aorta were measured. The association between these parameters and subsequent MACEs was performed by Cox proportional hazard models. RESULTS: Ten participants had subsequently MACEs. The Vpeak and PG gradually decreased and the WSS, PWV and EL progressively increased at 3 and 6 months compared with baseline. Adjusted multivariable analysis showed that the WSS of the proximal, mid- and distal ascending aorta [HR, 1.314 (95% confidence interval (CI): 1.003, 1.898)], [HR, 1.320 (95% CI: 1.002, 1.801)] and [HR, 1.322 (95% CI: 1.001, 1.805)] and PWV of ascending aorta [HR, 2.223 (95% CI: 1.010, 4.653)] at 3 months were associated with subsequent MACEs. Combined WSS and PWV of ascending aorta at 3 months yielded the highest AUC (0.912) for predicting subsequent MACEs. CONCLUSION: Combined WSS and PWV of ascending aorta at 3 months is helpful for predicting the subsequent MACEs in breast cancer patients treated by anthracyclines.