The association of arterial stiffness index with cerebrovascular and cardiometabolic disease: A Mendelian randomization study

Background: Arterial stiffness index (ASI) is a potential risk factor for cerebrovascular and cardiometabolic diseases, but the causal links between them are inconclusive. The aim is to evaluate the causal effects of ASI on cerebrovascular and cardiometabolic diseases by Mendelian randomization (MR). Methods: Two-sample MR analysis was performed to infer causal links. Genetic variants significantly associated with ASI were extracted. The inverse variance weighted method was used for estimating the effects. Sensitivity analysis was performed to test heterogeneity or pleiotropy. Results: MR analysis indicated an effect of genetically predicted ASI on the risk of ischemic stroke (IS) of all causes (OR = 1.894, 95% CI 1.210–2.965, p = 0.005). No links were identified between genetically predicted ASI and other cerebrovascular or cardiometabolic diseases (all p > 0.05). Subgroup analysis of IS etiologies found a suggestive association between genetically predicted ASI and large artery atherosclerosis stroke (LAS) (OR = 3.726, 95% CI 1.230–11.286, p = 0.020). There were no effects of ASI on IS due to cardioembolism or small vessel occlusion. Conclusion: The current MR analysis suggested that genetically predicted ASI was associated with higher risk of IS of all causes. The results and the underlying pathways or mechanisms between ASI and IS needs further investigation.

93 Melatonin and oxidative stress in the prevention of cardiovascular disease

Aims Arterial hypertension, especially if not well-controlled, is one of the main risk factors predisposing to fatal cardiovascular diseases (CVDs). Moreover, the diagnosis of essential hypertension are increasing, therefore oxidative stress and chronic inflammation have also been identified as potential responsible for the development of endothelial damage. Among all the molecules, melatonin (MT) was chosen for its role as a powerful antioxidant and anti-inflammatory endogenous molecule. This trial aims to evaluate the early intervention at the base of the inflammatory and oxidative cascade (that results in the development of hypertension), to restore an oxidative balance leading to positive results even at the endothelial and vascular level using MT in addition to anti-hypertensive therapy. Methods The trial is randomized, prospective and monocentric control. We enrolled 23 patients with hypertension in absence of other cardiovascular or autoimmune diseases that could alter the oxidative background, from March 2018 to April 2019 (recruitment period). Patients were randomly assigned to two groups: ‘melatonin group’ (in which 16 patients add 1 mg/day of melatonin for a year, to their already settled therapy), and a ‘control’ group (consisting of 7 patients with no changes in their therapy). The average follow-up was 1 year from randomisation. Patients were evaluated before and after a period of 1 year through MT plasma concentration and serum antioxidant capacity (TAC) by specific quantitative ELISA method. Therefore endothelial dysfunction and arterial stiffness were evaluated too (using the non-invasive methods of EndoPAT and SphygmoCor). Results In ‘melatonin group’ arterial stiffness index statistically decreased (P 0.022), according to a significant increase in plasma melatonin values (P 0.003) and significant decrease in TAC levels (P 0.041) despite the ‘control’ group. The improvement of endothelial function was not significant (P 0.688). Blood pressure had not a significative improvement too (P 0.401). Conclusions Data obtained could confirm the hypothesis of activation of plasma antioxidant system against a situation of altered oxidative balance. In fact, it is possible to hypothesize a correlation between TAC and arterial stiffness that confirm the antioxidant role of MT. The combination between antihypertensive therapy and antioxidant supplementation is able to improve the vascular stiffness. Data obtained are still preliminary and present some limitations but we can think of proposing this trial as a future basis for other extensive and prolonged studies.

The relationship between arterial stiffness index and coronary heart disease and its severity

Background Arterial stiffness index (ASI) is closely related to coronary atherosclerosis. This study aims to explore whether ASI can predict coronary heart disease (CHD) and its severity. Methods In this study, a total of 726 patients with suspected CHD were recruited. Based on coronary angiography results, the subjects were assigned into three groups: the control group (without obvious coronary artery disease), single-vessel disease group, and multi-vessel disease group (the number of vessels diseased ≥ 2). At the same time, according to the results of angiography, myocardial enzyme spectrum, electrocardiogram, color Doppler echocardiography and clinical manifestations, these patients were divided into four groups: the control group, stable angina (SA) Group, unstable angina (UA) group, and acute myocardial infarction (AMI) group. We have compared whether there were differences in ASI and related baseline data between groups. Receiver operating curve (ROC) analysis was conducted to determine whether ASI could predict CHD and evaluate the severity. Results ASI was positively correlated with the number of diseased branches of coronary artery. The value of ASI was increased as the number of the diseased branches increased. The ASI value in the SA group was significantly higher compared with the control group. Furthermore, the ASI value in the UA and AMI groups was remarkably increased compared with the control and SA groups. The results of ROC analysis indicated that the sensitivity and specificity of ASI was 71.0% and 85.4% in diagnosing CHD, respectively. While ASI was used in predicting the severity of CHD, the sensitivity was 72.1% and specificity 57.9%. Conclusion ASI is of great value in the diagnosis of coronary heart disease and the prediction of its severity.

Parameters of arterial stiffness in hypertensive patients with and without subclinical carotid atherosclerosis

Objective. To assess the relationship between arterial stiffness parameters in hypertensive patients with and without atherosclerotic lesions.Design and methods. We included 127 subjects who were divided into 3 groups: patients with hypertension (HTN) without atherosclerosis (n = 42); patients with HTN and subclinical atherosclerosis (SА) (n = 52) and control group which consisted of individuals without HTN, SA, or coronary artery disease (n = 33). All groups matched by age and gender. All subjects underwent following examinations: ultrasonography of extracranial segments of carotid arteries, 24-hour blood pressure monitoring with the assessment of arterial stiffness parameters.Results. In subjects with HTN compared to controls, pulse wave velocity in aorta (PWVao) was significantly higher (11,3 ± 1,5; 12,3 ± 1,8 vs 10,4 ± 1,3 m/s; p < 0,05), as well as pulse pressure (PP) (46,4 ± 9,8; 45,6 ± 10,6 vs 39,9 ± 6,5 mmHg; p < 0,05), central pulse pressure (PPао) (35,5 ± 8,5; 34,9 ± 8,5 vs 30,9 ± 5,4 mmHg; p < 0,05), and arterial stiffness index (ASI) (141 (127, 159); 139 (128,5, 160,5) vs 126 (118, 138) mmHg; p < 0,05). In subjects with HTN and SA, PWVao was significantly higher compared to other groups (p < 0,05). No significant difference in augmentation index was found (–32,5 (–45, –12); –22 (–36, –12); –37 (–50, –17); p = 0,25). Аmbulatory arterial stiffness index was higher in controls (0,5 ± 0,2) compared to HTN group (0,4 ± 0,2; p = 0,05), while HTN and SA group did not differ significantly (0,5 ± 0,2; p = 0,3). PWVao above 11,15 m/s is associated with 4,3 (2,3–8,2) times higher rate of atherosclerosis plaque detection.Conclusions. In HTN patients, arterial stiffness is changed compared to healthy individuals. PWVao above 11,15 m/s is associated with 4,3 (2,3–8,2) times higher rate of atherosclerosis plaque detection. In patients with HTN and SA arterial stiffness is higher, which might have additional predictive value in risk stratification.

Increased ambulatory arterial stiffness index and blood pressure load in normotensive obese patients

Objectives: It has been shown that blood pressure (BP) values measured in obese subjects are higher than the individuals with normal weight, even in normotensive limits. However, data concerning the Ambulatory Arterial Stiffness Index (AASI) and blood pressure load in normotensive obese subjects is lacking. This study was aimed to compare the ambulatory arterial stiffness index and blood pressure load in normotensive obese and healthy controls. Methods: One hundred normotensive obese and one hundred normal weight subjects were included in this study. All sub- jects underwent 24-hour ambulatory blood pressure monitoring. Ambulatory arterial stiffness index was calculated from 24-hour ambulatory blood pressure monitoring records. Ambulatory arterial stiffness index was defined as one minus the regression slope of unedited 24-h diastolic on systolic blood pressures. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) load values were calculated from 24-hour ambulatory blood pressure monitoring analysis. Results: Ambulatory arterial stiffness index of the obese subjects was significantly higher than the healthy controls (0.48±0.2 vs. 0.33±0.11, p<0.001). 24-hours systolic blood pressure and diastolic blood pressure loads were significantly higher in obese subjects. Logistic regression analysis revealed that body mass index (BMI) was an independent predictor for an abnor- mal ambulatory arterial stiffness ındex (≥0.50) (OR: 1.137, 95% CI: 0.915-1.001, p=0.004). Conclusion: Blood pressure load and ambulatory arterial stiffness index are increased in normotensive obese patients. Moreover, body mass index is an independent predictor for an abnormal ambulatory arterial stiffness index. Our results indicate that obese subjects are at higher risk for future cardiovascular events despite normal office BP levels. Keywords: Ambulatory arterial stiffness index; blood pressure load; obesity; blood pressure.

Age-associated changes in vascular health and its relation with erythropoietin

Objectives: Vascular stiffness due to ageing assessed by alteration in mean arterial blood pressure, brachial-ankle and carotid-femoral pulse wave velocity (b-f PWV/c-f PWV) and brachial and ankle arterial stiffness index (ASI). The present study aimed to determine the influence of ageing on vascular health and its relation to oxygen sensing protein that is, erythropoietin (EPO), in both genders (men and women). Materials and Methods: Randomly selected 204 healthy participants involving men and women between 20 and 95 years among the general population of city. The total sample size was split into six groups from Group I to VI, each containing 17 men participants and 17 women participants. We determined PWV [brachial-ankle and carotid-femoral (PWV)] and ASI (brachial ASI and ankle ASI) by using periscope and estimated serum erythropoietin (Epo) by ELISA method and implemented a one-way ANOVA post hoc test for statistical analysis by using SPSS software version 23. Results: Decreased serum EPO with increased vascular parameters such as mean arterial pressure (MAP), PWV and ASI observed in Group 5 and 6 of both genders. Conclusion: We conclude that ageing influences PWV, ASI, MAP and EPO in men and women participants.

Assessment of the effectiveness of antihypertensive therapy in the early post-stroke period of ischemic stroke based on indicators of arterial stiffness

Funding Acknowledgements Type of funding sources: None. Introduction Globally, stroke is the second leading cause of death, leading to a reduction in life expectancy and disability of patients. It seems important to study and introduce into practical health care both new approaches to stroke prevention and measures aimed at full recovery in the post-stroke period. Purpose To assess the antihypertensive therapy (AHT) in patients with arterial hypertension (AH) in the early post-stroke period of ischemic stroke (IS), based on indicators of arterial stiffness. Methods The study included 180 patients with hypertension (mean age 64 years) in the acute period of ischemic stroke (IS). Inclusion criteria in this trial: AH, age over 40 years, time from the onset of stroke no more than 48 hours. Arterial stiffness was assessed by an oscillometric method with an assessment of the 24-hour reflected wave transit time (RWTT), aortic augmentation index (AIxao)), arterial stiffness index (ASI), and pulse wave velocity (PWV). The indicators were assessed at the time of admission, at the time of discharge from the hospital (14-21 days) and 2 months after discharge. We determined endothelin-1 (ET-1) levels by ELISA at admission and 2 months after discharge. Retrospectively, patients were divided into 5 groups depending on the prescribed AHT: group 1 (48 patients) - ACEIs/ARBs, thiazide-like diuretics (TLDs), group 2 (46 people) - ACEIs/ARBs, nondihydropyridine calcium antagonists (ACs) and beta-blockers (BBs), group 3 (39 people) - ACEIs/ARBs and ACs, group 4 (26 patients) - ACEIs/ARBs and BBs, group 5 (21 people) - ACEIs/ARBs, TLDs and BBs. Results AHT showed a positive trend in terms of arterial stiffness in all 5 groups. Compared with the baseline values, the significant decrease in PWV (12.4 ± 1.7m/s vs 10.9 ± 1.8m/s, p &lt; 0.01), AIxao (39.8 ± 6.3% vs 36.8 ± 5,2%, p &lt; 0.001), ASI (167.9(127.0;174.5) vs 158.8(115.0;168.7)), p &lt; 0.05), increased RWTT (98.0 ± 9.8ms vs 105.3 ± 7.5ms) in group 2 of patients were found. After 2 months, when comparing indicators between groups the significant decrease in PWV to 9.1(8.7; 11.6)m/s, p &lt; 0.01), AIxao to 31.7(29.8;41.9)%, p &lt; 0.01, an increase in RWTT to 107.7(102.4; 110.2)ms, p &lt; 0.01 in the group of patients taking ACEIs/ARBs, ACs and BBs were detected. After 2 months after discharge, a significant decrease of ET-1 was also observed in group 2 (5.8 ± 2.2ng/ml vs 4.2 ± 1.8ng/ml). The combination of ACEs/ARBs and BBs showed the least effectiveness in reducing arterial stiffness. Conclusions The combination of ACEIs/ARBs, ACs and BBs showed the greatest efficiency in reducing the stiffness in patients with hypertension in the early post-stroke period of IS. It seems important for the functional recovery of patients in the post-stroke period to use the drug therapy aimed not only at lowering blood pressure, but also favorably affecting the arterial stiffness.