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ABCA1 Polymorphism Is Associated With the Warfarin-Induced Aortic Stiffness After Coronary Artery Bypass Surgery in the Chinese Population.
Liao, S, Zhou, Q, Zhang, Y
Journal of cardiovascular pharmacology. 2020;(3):360-366
Abstract
Warfarin is the most widely prescribed oral anticoagulant and is recommended for patients recovering from coronary artery bypass graft (CABG) with atrial fibrillation. Increasing evidence suggested that warfarin increased arterial stiffness in those patients. We aimed to examine the effect of warfarin therapy on aortic stiffness in patients who underwent CABG with or without postoperative warfarin treatment and explored the potential relationships of warfarin therapy with ABCA1 polymorphisms. This was a retrospect observational study of 24 patients who were continuously treated with warfarin were selected as the warfarin group and matched them by age (±3 years) and gender to 48 patients with nonuse of warfarin as the control group. The aortic stiffness, cholesterol efflux capacity, and plasma level of PIVKA-II were measured. Two ABCA1 polymorphisms were genotyped. Compared with baseline, treatment with warfarin for 1 year significantly increased the plasma level of PIVKA-II and aortic stiffness in pulse pressure and pulse wave velocity in patients after CABG. The increase of pulse wave velocity and plasma PIVKA-II level in the TT genotype was significantly greater than the CC genotype when comparing the -565C/T genotypes. The capacity of cholesterol efflux was significantly lower in the TT genotype at baseline and 1-year follow-up than the CC genotype. Postoperative treatment of warfarin for 1 year significantly increased aortic stiffness in patients who underwent CABG. ABCA1 -565C/T polymorphisms affected the cholesterol efflux capacity and were associated with the vitamin K status and the increased aortic stiffness after warfarin treatment in those patients.
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Brachial-Ankle Pulse Wave Velocity Versus Its Stiffness Index β-Transformed Value as Risk Marker for Cardiovascular Disease.
Tomiyama, H, Ohkuma, T, Ninomiya, T, Nakano, H, Matsumoto, C, Avolio, A, Kohro, T, Higashi, Y, Maruhashi, T, Takase, B, et al
Journal of the American Heart Association. 2019;(24):e013004
Abstract
Background The difference in the predictive ability of the brachial-ankle pulse wave velocity (baPWV) and its stiffness index β-transformed value (β-baPWV, ie, baPWV adjusted for the pulse pressure) for the development of pathophysiological abnormalities related to cardiovascular disease or future occurrence of cardiovascular disease was examined. Methods and Results In study 1, a 7-year prospective observational study in cohorts of 3274 men and 3490 men, the area under the curve in the receiver operator characteristic curve analysis was higher for baPWV than for β-baPWV for predicting the development of hypertension (0.73, 95% CI=0.70 to 0.75 versus 0.59, 95% CI=0.56 to 0.62; P<0.01) and/or the development of retinopathy (0.78, 95% CI=0.73 to 0.82 versus 0.66, 95% CI=0.60 to 0.71; P<0.01) by the end of the study period. During study 2, a 3-year observation period on 511 patients with coronary artery disease, 72 cardiovascular events were confirmed. The C statistics of both markers for predicting the development of cardiovascular events were similar. Conclusions Stiffness index β transformation of the baPWV may attenuate the significance of the baPWV as a risk marker for development of pathophysiological abnormalities related to cardiovascular disease in male subjects.
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Effect of 12-month intervention with low-dose atorvastatin on pulse wave velocity in subjects with type 2 diabetes and dyslipidaemia.
Grigoropoulou, P, Tentolouris, A, Eleftheriadou, I, Tsilingiris, D, Vlachopoulos, C, Sykara, M, Tentolouris, N
Diabetes & vascular disease research. 2019;(1):38-46
Abstract
Cardiovascular disease is the leading cause of morbidity and mortality in subjects with type 2 diabetes mellitus. Increased aortic stiffness, assessed with the carotid-femoral pulse wave velocity, is an independent risk factor for cardiovascular disease. Statins reduce effectively cardiovascular disease and mortality in high-risk patients. The aim of this prospective non-randomized, observational study was to examine the impact of treatment with either 10 mg atorvastatin plus diet or diet alone on carotid-femoral pulse wave velocity in subjects with type 2 diabetes mellitus and dyslipidaemia. A total of 79 subjects with type 2 diabetes mellitus and dyslipidaemia were included; 46 subjects were treated with atorvastatin 10 mg daily plus diet and 33 were managed by diet alone for 12 months. Carotid-femoral pulse wave velocity and carotid-radial pulse wave velocity were measured using applanation tonometry. In the atorvastatin-treated group, carotid-femoral pulse wave velocity reduced significantly during the study and there was a trend for reduction in the carotid-radial pulse wave velocity. Total cholesterol, low-density lipoprotein cholesterol, triglycerides and C-reactive protein were reduced only in the atorvastatin-treated participants. No significant changes were found in body mass index, blood pressure, heart rate, diabetes control and high-density lipoprotein cholesterol in either study group. Treatment with low-dose atorvastatin for 12 months improves carotid-femoral pulse wave velocity in subjects with type 2 diabetes mellitus and dyslipidaemia.
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Empagliflozin on top of metformin treatment improves arterial function in patients with type 1 diabetes mellitus.
Lunder, M, Janić, M, Japelj, M, Juretič, A, Janež, A, Šabovič, M
Cardiovascular diabetology. 2018;(1):153
Abstract
BACKGROUND Deteriorated arterial function and high incidence of cardiovascular events characterise diabetes mellitus. Metformin and recent antidiabetic drugs, SGLT2 inhibitors, reduce cardiovascular events. We explored the possible effects of empagliflozin's effect on top of metformin treatment on endothelial function and arterial stiffness parameters in type 1 diabetes mellitus (T1DM) patients. METHODS Forty T1DM patients were randomised into three treatment groups: (1) empagliflozin (25 mg daily), (2) metformin (2000 mg daily) and (3) empagliflozin/metformin (25 mg daily and 2000 mg daily, respectively). The fourth group received placebo. Arterial function was assessed at inclusion and after 12 weeks treatment by: endothelial function [brachial artery flow-mediated dilation (FMD), reactive hyperaemia index (RHI)], arterial stiffness [pulse wave velocity (PWV) and common carotid artery stiffness (β-stiffness)]. For statistical analysis one-way analysis of variance with Bonferroni post-test was used. RESULTS Empagliflozin on top of metformin treatment significantly improved endothelial function as did metformin after 12 weeks of treatment: FMD [2.6-fold (P < 0.001) vs. 1.8-fold (P < 0.05)] and RHI [1.4-fold (P < 0.01) vs. 1.3-fold (P < 0.05)]. Empagliflozin on top of metformin treatment was superior to metformin in improving arterial stiffness parameters; it significantly improved PWV and β-stiffness compared to metformin [by 15.8% (P < 0.01) and by 36.6% (P < 0.05), respectively]. Metformin alone did not influence arterial stiffness. CONCLUSION Empagliflozin on top of metformin treatment significantly improved arterial stiffness compared to metformin in T1DM patients. Endothelial function was similarly improved in all treatment groups. Empagliflozin seems to possess a specific capacity to decrease arterial stiffness, which could support its cardioprotective effects observed in large clinical studies. Trial registration Clinical trial registration: NCT03639545.
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Effect of Low (5 mg) vs. High (20-40 mg) Rosuvastatin Dose on 24h Arterial Stiffness, Central Haemodynamics, and Non-Alcoholic Fatty Liver Disease in Patients with Optimally Controlled Arterial Hypertension.
Mitsiou, E, Boutari, C, Kotsis, V, Georgianou, E, Doumas, M, Karagiannis, A, Athyros, VG
Current vascular pharmacology. 2018;(4):393-400
Abstract
OBJECTIVE Arterial Stiffness (AS) and Non-Alcoholic Fatty Liver Diseases (NAFLD) are 2 related, prevalent, risk predictors of Cardiovascular Disease (CVD). We assessed the effect of low dose (5 mg/day) vs. high dose (20-40 mg/day) rosuvastatin on aortic elasticity and central haemodynamics as well as on NAFLD in patients with Arterial Hypertension (AH). METHODS Forty patients with optimally controlled AH were randomised to 2 rosuvastatin doses and followed for 6 months. 24h AS was assessed by Mobil-O-Graph, which calculates (adjusted for age and gender) Pulse Wave Velocity (PWV), adjusted for Heart Rate (HR) augmentation index (AIx75%) and central haemodynamics. The diagnosis of NAFLD was based on >5% liver steatosis on ultrasound and moderately elevated serum levels of liver enzymes. RESULTS Both doses of rosuvastatin reduced Central Pulse Pressure (cPP), PWV and AIx75% (adjusted for HR) to normal values (p = NS adjusted for age, gender and HR). Liver enzymes were reduced in those with NAFLD to normal, but steatosis was reduced more by the 20-40 mg/day rosuvastatin dose (p=0.01) compared with the 5 mg/day dose. CONCLUSION Both doses of rosuvastatin had a beneficial effect on AS; the high dose was more efficient in reducing PWVs and central haemodynamics, and also the high dose was more effective in ameliorating NAFLD. Given that AH control was optimal and lipid values attained targets, 4 other CVD predictors were also addressed. Larger and longer term studies are needed to demonstrate the clinical benefit of such treatment preference.
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The effect of sacubitril/valsartan compared to olmesartan on cardiovascular remodelling in subjects with essential hypertension: the results of a randomized, double-blind, active-controlled study.
Schmieder, RE, Wagner, F, Mayr, M, Delles, C, Ott, C, Keicher, C, Hrabak-Paar, M, Heye, T, Aichner, S, Khder, Y, et al
European heart journal. 2017;(44):3308-3317
Abstract
AIMS: Progressive aortic stiffening eventually leads to left ventricular (LV) hypertrophy and heart failure if left untreated. Anti-hypertensive agents have been shown to reverse this to some extent. The effects of sacubitril/valsartan (LCZ696), a dual-action angiotensin receptor blocker (ARB), and neprilysin inhibitor, on arterial stiffness and LV remodelling have not been investigated. METHODS AND RESULTS This was a randomized, multi-centre, double-blind, double-dummy, active-controlled, parallel group, study to compare the effects on cardiovascular remodelling of sacubitril/valsartan with those of olmesartan in patients with hypertension and elevated pulse pressure. Magnetic resonance imaging scans were used to assess LV mass and local aortic distensibility, at baseline and at 12 and 52 weeks after initiation of treatment. Central pulse and systolic pressure were determined using a SphymoCor® XCEL device at each time point. A total of 114 patients were included, with 57 in each treatment group. The mean age was 59.8 years, and 67.5% were male. Demographic characteristics did not vary between the two sets of patients. Left ventricular mass index decreased to a greater extent in the sacubitril/valsartan group compared to the olmesartan group from baseline to 12 weeks (-6.36 vs. -2.32 g/m2; P = 0.039) and from baseline to 52 weeks (-6.83 vs. -3.55 g/m2; P = 0.029). These differences remained significant after adjustment for systolic blood pressure (SBP) at follow-up (P = 0.036 and 0.019 at 12 and 52 weeks, respectively) and similar signals (though formally non-significant) were observed after adjusting for changes in SBP (P = 0.0612 and P = 0.0529, respectively). There were no significant differences in local distensibility changes from baseline to 12 or 52 weeks between the two groups; however, there was a larger reduction in central pulse pressure for the sacubitril/valsartan group compared to the olmesartan group (P = 0.010). CONCLUSION Since LV mass change correlates with cardiovascular prognosis, the greater reductions in LV mass indicate valuable advantages of sacubitril/valsartan compared to olmesartan. The finding that LV mass index decrease might be to some extent independent of SBP suggests that the effect of the dual-acting agent may go beyond those due to its BP-lowering ability.
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High trans but not saturated fat beverage causes an acute reduction in postprandial vascular endothelial function but not arterial stiffness in humans.
Lane-Cordova, AD, Witmer, JR, Dubishar, K, DuBose, LE, Chenard, CA, Siefers, KJ, Myers, JE, Points, LJ, Pierce, GL
Vascular medicine (London, England). 2016;(5):429-436
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Abstract
A diet high in trans-fatty acids (TFAs) is associated with a higher risk of cardiovascular disease (CVD) than a diet high in saturated fatty acids (SFAs), but the mechanisms remain unclear. We hypothesized that a beverage high in TFAs would cause a larger reduction in postprandial endothelial function and an increase in arterial stiffness, in part from greater reductions in insulin sensitivity, compared with a beverage high in SFAs. Eleven healthy adults (aged 47±5 years) ingested a warm test beverage (520 kcal, 56 g total fat, 5 g carbohydrate, 1 g protein) high in either TFAs or SFAs in a randomized cross-over study. Ingestion of the beverage high in TFAs (p<0.01) but not high in SFAs (p=0.49) decreased endothelial function (brachial artery flow-mediated dilation, mmΔ) at 3-4 hours (p<0.01 for time; p=0.034 for interaction), but did not alter aortic stiffness or carotid β-stiffness. The homeostasis model of insulin resistance (interaction p=0.062) tended to decrease after SFAs but not TFAs. A beverage high in TFAs but not SFAs results in a postprandial reduction in endothelial function and a trend for decreased insulin sensitivity, potentially explaining the higher risk of CVD with a diet high in TFAs.
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Anagliptin, A Dipeptidyl Peptidase-4 Inhibitor Ameliorates Arterial Stiffness in Association with Reduction of Remnant-Like Particle Cholesterol and Alanine Transaminase Levels in Type 2 Diabetic Patients.
Tahara, N, Yamagishi, SI, Bekki, M, Kodama, N, Nakamura, T, Sugiyama, Y, Oshige, T, Kumashiro, Y, Honda, A, Tahara, A, et al
Current vascular pharmacology. 2016;(6):552-562
Abstract
BACKGROUND Inhibition of dipeptidyl peptidase-4 (DPP-4) has been proposed as a therapeutic target for type 2 diabetes (T2DM). Arterial stiffness, a predictor of future cardiovascular events and all-cause mortality, is augmented in these patients. However, effects of DPP-4 inhibitors on arterial stiffness remain unknown. In this study, we compared effects of anagliptin, an inhibitor of DPP-4 on arterial stiffness evaluated by cardio-ankle vascular index (CAVI) with those of an equipotent glucose-lowering agent, glimepiride in patients with T2DM. METHODS The study involved 50 consecutive outpatients (33 males and 17 females; mean age of 72.5±9.5 years) who visited our hospitals for a risk-screening test or treatment for T2DM. They underwent complete history and physical examination, and determination of blood chemistry and anthropometric variables, and then were randomized to receive either anagliptin (n=26) or glimepiride (n=24) for 6 months. RESULTS After 6-months treatment, fasting plasma glucose and HbA1c values were comparably reduced in both groups. Anagliptin, but not glimepiride treatment significantly decreased low-density lipoprotein cholesterol, malondialdehyde-modified LDL, remnant-like particle (RLP) cholesterol, CAVI, alanine transaminase (ALT), γ-glutamyl transferase and visceral fat volume. In multiple regression analysis, absolute changes from baseline of RLP cholesterol and ALT after anagliptin treatment for 6 months (ΔRLP cholesterol and ΔALT) were independently correlated with ΔCAVI (R2=0.445). CONCLUSION The present study suggests that anagliptin may exert a beneficial effect on arterial stiffness in patients with T2DM, which is independent of its blood glucose-lowering property. Anagliptin may ameliorate arterial stiffness partly via reduction of RLP cholesterol and improvement of liver function.
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Effects of combined aerobic and resistance exercise on central arterial stiffness and gait velocity in patients with chronic poststroke hemiparesis.
Lee, YH, Park, SH, Yoon, ES, Lee, CD, Wee, SO, Fernhall, B, Jae, SY
American journal of physical medicine & rehabilitation. 2015;(9):687-95
Abstract
OBJECTIVE The effects of combined aerobic and resistance exercise training on central arterial stiffness and gait velocity in patients with chronic poststroke hemiparesis were investigated. DESIGN Twenty-six patients with chronic poststroke hemiparesis were randomly assigned to either the combined aerobic and resistance exercise group (n = 14) or the control group (n = 12). The exercise intervention group received a combined aerobic and resistance exercise training (1 hr/day, three times/week for 16 wks), whereas the control group received usual care. Central arterial stiffness was determined by pulse wave velocity and augmentation index. Gait velocity was assessed using the 6-min walk test, 10-m walk test, and the Timed Up-and-Go test. RESULTS Patients in the exercise intervention group had greater improvement of mean pulse wave velocity (P < 0.001), augmentation index (P = 0.048), and gait velocity (6-min walk test, P < 0.001; 10-m walk test, P < 0.001) than did patients in the control group. Patients in the exercise intervention group also had greater improvements in physical fitness component (grip strength, P < 0.001; muscular strength of upper and lower limbs, P < 0.027; flexibility, P < 0.001) when compared with control patients. CONCLUSIONS The combined aerobic and resistance exercise program significantly reduced central arterial stiffness and increased gait velocity in patients with chronic poststroke hemiparesis.
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The effect of aliskiren versus ramipril-based treatment on the Ambulatory Arterial Stiffness Index in hypertensive patients.
Andreadis, EA, Angelopoulos, ET, Kolyvas, GN, Agaliotis, GD, Mousoulis, CG, Mousoulis, GP
International angiology : a journal of the International Union of Angiology. 2014;(1):78-83
Abstract
AIM: Aim of the present study was to compare the effectiveness of two renin-angiotensin-aldosterone system inhibitors in arterial stiffness reduction in previously untreated hypertensive patients. METHODS In this open label study, 154 naïve, or not treated in the last six months hypertensive patients were randomly assigned to receive aliskiren 300 mg or ramipril 5 mg daily. Six weeks after the initiation of treatment, patients were evaluated for blood pressure (BP) control. Patients with SBP ≥140 and/or DBP ≥90 mmHg were assigned to an adjunct of 25 mg hydrochlorothiazide as combination treatment. A re-evaluation of BP control was done after another 6 weeks. Individuals with BP ≥140/90 mmHg were further administered amlodipine 5 mg. The final evaluation was performed six months after the start of the study. Twenty four-hour ambulatory blood pressure monitoring was carried out and the ambulatory arterial stiffness index (AASI) was calculated at baseline and after 6 months of treatment. RESULTS Aliskiren-based therapy, as compared with ramipril-based therapy reduced BP to a similar degree: 13±11 vs. 12±11 mmHg reduction in systolic (P=0.34) and 8±7 vs. 7±7 mmHg reduction in diastolic BP (P=0.44). AASI was reduced by 0.04±0.1 in the aliskiren group and by 0.02±0.2 in the ramipril group. AASI reduction did not differ significantly in the two groups (P=0.13). CONCLUSION In hypertensive patients, aliskiren-based treatment as well as ramipril-based treatment appears to have a beneficial effect on arterial stiffness. As arterial stiffness is an important modifiable risk factor, our findings highlight the value of aliskiren beyond BP lowering properties.