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Mediterranean-Style Diet Improves Systolic Blood Pressure and Arterial Stiffness in Older Adults.
Jennings, A, Berendsen, AM, de Groot, LCPGM, Feskens, EJM, Brzozowska, A, Sicinska, E, Pietruszka, B, Meunier, N, Caumon, E, Malpuech-Brugère, C, et al
Hypertension (Dallas, Tex. : 1979). 2019;(3):578-586
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Abstract
We aimed to determine the effect of a Mediterranean-style diet, tailored to meet dietary recommendations for older adults, on blood pressure and arterial stiffness. In 12 months, randomized controlled trial (NU-AGE [New Dietary Strategies Addressing the Specific Needs of Elderly Population for Healthy Aging in Europe]), blood pressure was measured in 1294 healthy participants, aged 65 to 79 years, recruited from 5 European centers, and arterial stiffness in a subset of 225 participants. The intervention group received individually tailored standardized dietary advice and commercially available foods to increase adherence to a Mediterranean diet. The control group continued on their habitual diet and was provided with current national dietary guidance. In the 1142 participants who completed the trial (88.2%), after 1 year the intervention resulted in a significant reduction in systolic blood pressure (-5.5 mm Hg; 95% CI, -10.7 to -0.4; P=0.03), which was evident in males (-9.2 mm Hg, P=0.02) but not females (-3.1 mm Hg, P=0.37). The -1.7 mm Hg (95% CI, -4.3 to 0.9) decrease in diastolic pressure after intervention did not reach statistical significance. In a subset (n=225), augmentation index, a measure of arterial stiffness, was improved following intervention (-12.4; 95% CI, -24.4 to -0.5; P=0.04) with no change in pulse wave velocity. The intervention also resulted in an increase in 24-hour urinary potassium (8.8 mmol/L; 95% CI, 0.7-16.9; P=0.03) and in male participants (52%) a reduction in pulse pressure (-6.1 mm Hg; 95% CI, -12.0 to -0.2; P=0.04) and 24-hour urinary sodium (-27.1 mmol/L; 95% CI, -53.3 to -1.0; P=0.04). In conclusion, a Mediterranean-style diet is effective in improving cardiovascular health with clinically relevant reductions in blood pressure and arterial stiffness. Clinical Trial Registration- URL: http://www.clinicialtrials.gov . Unique identifier: NCT01754012.
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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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How does empagliflozin improve arterial stiffness in patients with type 2 diabetes mellitus? Sub analysis of a clinical trial.
Bosch, A, Ott, C, Jung, S, Striepe, K, Karg, MV, Kannenkeril, D, Dienemann, T, Schmieder, RE
Cardiovascular diabetology. 2019;(1):44
Abstract
BACKGROUND Empagliflozin has been shown to reduce cardiovascular mortality, but the underlying pathogenetic mechanisms are poorly understood. It was previously demonstrated that empagliflozin improved arterial stiffness. METHODS Our analysis comprising 58 patients with type 2 diabetes mellitus identifies factors triggering the improvement of arterial stiffness. All patients participated in an investigator-initiated, prospective, double-blind, randomized, placebo-controlled, interventional clinical trial ( http://www.ClinicalTrials.gov : NCT02471963, registered 15th June 2015, retrospectively registered) and received either 6-weeks treatment with 25 mg empagliflozin orally once daily or placebo (crossover). Central systolic pressure and central pulse pressure were recorded by the SphygmoCor System (AtCor Medical). Now, we investigated the impact of parameters of glucose metabolism, volume status, sympathetic activation, lipids, uric acid, blood pressure and inflammation on vascular parameters of arterial stiffness using multivariate regression analysis. RESULTS As previously reported, therapy with empagliflozin improved arterial stiffness as indicated by reduced central systolic blood pressure (113.6 ± 12.1 vs 118.6 ± 12.9 mmHg, p < 0.001), central pulse pressure (39.1 ± 10.2 vs 41.9 ± 10.7 mmHg, p = 0.027) forward (27.1 ± 5.69 vs 28.7 ± 6.23 mmHg, p = 0.031) as well as reflected wave amplitude (18.9 ± 5.98 vs 20.3 ± 5.97 mmHg, p = 0.045) compared to placebo. The multivariate regression analysis included age, sex and change between empagliflozin and placebo therapy of the following parameters: HbA1c, copeptin, hematocrit, heart rate, LDL-cholesterol, uric acid, systolic 24-h ambulatory blood pressure and high sensitive CRP (hsCRP). Besides the influence of age (beta = - 0.259, p = 0.054), sex (beta = 0.292, p = 0.040) and change in systolic 24-h ambulatory blood pressure (beta = 0.364, p = 0.019), the change of hsCRP (beta = 0.305, p = 0.033) emerged as a significant determinant of the empagliflozin induced reduction in arterial stiffness (placebo corrected). When replacing HbA1c with fasting plasma glucose in the multivariate regression analysis, a similar effect of the change in hsCRP (beta = 0.347, p = 0.017) on arterial stiffness parameters was found. CONCLUSION Besides age and sex, change in systolic 24-h ambulatory blood pressure and change in hsCRP were determinants of the empagliflozin induced improvement of vascular parameters of arterial stiffness, whereas parameters of change in glucose metabolism and volume status had no significant influence. Our analysis suggests that empagliflozin exerts, at least to some extent, its beneficial vascular effects via anti-inflammatory mechanisms. Trial registration http://www.ClinicalTrials.gov : NCT02471963, registered 15th June 2015, retrospectively registered.
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Metformin use in type 2 diabetic patients is not associated with lower arterial stiffness: the Maastricht Study.
Driessen, JHM, de Vries, F, van Onzenoort, HAW, Schram, MT, van der Kallen, C, Reesink, KD, Sep, S, Stehouwer, CDA, Schaper, N, Kroon, AA, et al
Journal of hypertension. 2019;(2):365-371
Abstract
INTRODUCTION Type 2 diabetes (T2D) is associated with cardiovascular disease complications such as myocardial infarction and stroke. These complications are at least partially the consequence of diabetes-associated increased arterial stiffness. Metformin, a first choice oral glucose-lowering drug, has been associated with potential cardio-protective effects. However, there are no data on the association between real-life metformin use and arterial stiffness. The objective of the current study is to investigate in a population-based sample of individuals with T2D the association between metformin use and aortic stiffness (i.e. carotid-femoral pulse wave velocity, cfPWV) and carotid stiffness [i.e. carotid distensibility coefficient and Young's elastic modulus (YEM)]. METHODS We used data from The Maastricht Study, an ongoing observational prospective population-based cohort study (current N = 3451). All participants with T2D, based on pharmacy records (N = 672, 31.3% women, mean age 62.6 ± 7.7), were included in the current study. Linear regression analyses were used to study the association between current metformin use and cfPWV, distensibility coefficient and YEM, as compared with no metformin use. Furthermore, metformin use was stratified by cumulative dose (in grams), continuous duration of use (in days), average daily dose (in grams) and time since first prescription (in years). Regression coefficients of distensibility coefficient were multiplied by -1, consequently, for all arterial stiffness indices, a positive regression coefficient signifies increasing arterial stiffness. RESULTS Linear regression showed that neither current metformin use was associated with cfPWV [adjusted B: -0.04 (-0.11 to 0.02)] nor metformin use was as stratified by cumulative dose, by continuous duration of use, by average daily dose or by time since first prescription. Metformin use was statistically significantly associated with higher carotid stiffness as assessed by distensibility coefficient [0.12 (0.01 to 0.23)], but not with YEM [0.10 (-0.03 to 0.22)]. However, there was no consistent pattern with the different stratifications of metformin use when further investigating the association with distensibility coefficient. CONCLUSION We showed that there is no significant association between current metformin use and aortic stiffness, regardless of how metformin use in itself was defined. In addition, metformin use was not associated with a lower carotid stiffness. The present results showed no beneficial effect of metformin use, dosage or duration on arterial stiffness in middle-aged patients with T2D. Alternatively, metformin may exerts its cardio-protective effects via other pathways.
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Measurement of arterial stiffness and vascular aging in community pharmacies-The ASINPHAR@2action project.
Pereira, T, Paulino, E, Maximiano, S, Rosa, M, Pinto, AL, Mendes, MJ, Brito, J, Soares, P, Risse, J, Gose, S
Journal of clinical hypertension (Greenwich, Conn.). 2019;(6):813-821
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Abstract
The ASINPHAR@2action project aims at raising awareness to arterial stiffness (AS) and early vascular aging (EVA) through a community pharmacy-based intervention. This preliminary analysis is focused on the analysis of the proportion of participants with increased AS and the identification of its main determinants. We performed an observational cross-sectional study of participants enrolled in 11 community pharmacies in Portugal, between April and November 2017. Blood pressure (BP) and arterial function parameters were measured with a validated device. Clinical and demographic information was gathered, as well as the estimation of global cardiovascular risk, health-related quality of life, and dietary profile. Cholesterol and glycaemia were taken from a recent laboratory bulletin. The cohort includes 658 participants with a mean age of 57.3 ± 16.3 years, 66% women. Brachial BP was 126.6 ± 16.4 mm Hg and 79.9 ± 11.5 mm Hg, and central BP was 115.8 ± 15.4 mm Hg and 81.2 ± 11.6 mm Hg, respectively, for systolic and diastolic BP. Mean pulse wave velocity (PWV) was 8.5 ± 2.3 m/s, and the augmentation index was 23.6 ± 15.6%. The proportion of participants with increased AS was 19.8%. The overall best-fitting model for AS included age, gender, aortic PP, visceral fat, HDL cholesterol, AIx@75, total vascular resistance, hypertension, and diabetes, corresponding to an AUC of 0.910 (CI: 0.883, 0.937; P < 0.001) in the ROC curve analysis. The preliminary results of this pioneering large-scale study measuring arterial function in community pharmacies provide the grounds for the operationalization of subclinical target organ damage screening in pharmacies, as a strategy to improve cardiovascular risk monitoring and to promote adherence to treatment.
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Aortic and Systemic Arterial Stiffness Responses to Acute Exercise in Patients With Small Abdominal Aortic Aneurysms.
Perissiou, M, Bailey, TG, Windsor, M, Greaves, K, Nam, MCY, Russell, FD, O'Donnell, J, Magee, R, Jha, P, Schulze, K, et al
European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery. 2019;(5):708-718
Abstract
OBJECTIVE/BACKGROUND Elevated arterial stiffness is a characteristic of abdominal aortic aneurysm (AAA), and is associated with AAA growth and cardiovascular mortality. A bout of exercise transiently reduces aortic and systemic arterial stiffness in healthy adults. Whether the same response occurs in patients with AAA is unknown. The effect of moderate- and higher intensity exercise on arterial stiffness was assessed in patients with AAA and healthy adults. METHODS Twenty-two men with small diameter AAAs (36 ± 5 mm; mean age 74 ± 6 years) and 22 healthy adults (mean age 72 ± 5 years) were included. Aortic stiffness was measured using carotid to femoral pulse wave velocity (PWV), and systemic arterial stiffness was estimated from the wave reflection magnitude (RM) and augmentation index (Alx75). Measurements were performed at rest and during 90 min of recovery following three separate test sessions in a randomised order: (i) moderate intensity continuous exercise; (ii) higher intensity interval exercise; or (iii) seated rest. RESULTS At rest, PWV was higher in patients with AAA than in healthy adults (p < .001), while AIx75 and RM were similar between groups. No differences were observed between AAA patients and healthy adults in post-exercise aortic and systemic arterial stiffness after either exercise protocol. When assessed as the change from baseline (delta, Δ), post-exercise ΔAIx75 was not different to the seated rest protocol. Conversely, post-exercise ΔPWV and ΔRM were both lower at all time points than seated rest (p < .001). ΔPWV was lower immediately after higher intensity than after moderate intensity exercise (p = .015). CONCLUSION High resting aortic stiffness in patients with AAA is not exacerbated after exercise. There was a similar post-exercise attenuation in arterial stiffness between patients with AAA and healthy adults compared with seated rest. This effect was most pronounced following higher intensity interval exercise, suggesting that this form of exercise may be a safe and effective adjunctive therapy for patients with small AAAs.
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Effects of Simvastatin on Augmentation Index Are Transient: Outcomes From a Randomized Controlled Trial.
Gepner, AD, Lazar, K, Hulle, CV, Korcarz, CE, Asthana, S, Carlsson, CM
Journal of the American Heart Association. 2019;(20):e009792
Abstract
Background Statins improve endothelial function, but their effects on arterial stiffness and aortic blood pressure in middle-aged adults are uncertain. Methods and Results This was a prospective, randomized, double-blind, placebo-controlled trial of middle-aged (40-72 years old) adults who were randomly assigned to receive simvastatin 40 mg (n=44) or placebo (n=44) daily for 18 months to evaluate impact on dementia-related biomarkers (primary end points) and measures of vascular health (secondary end points). This analysis focuses on the predetermined secondary end points of changes in central aortic blood pressure, aortic augmentation index, and brachial artery flow-mediated dilation. Measurements were performed at baseline and after 6, 12, and 18 months. Multivariable models were used to identify predictors of these prespecified vascular end points. Study groups were similar at baseline; low-density lipoprotein cholesterol declined in the statin group but not in the placebo group (P<0.01). There were no significant differences in changes in central blood pressure parameters or flow-mediated dilation (all P>0.2). After 12 months, augmentation index decreased from baseline in the statin group compared with the placebo group (-2.3% [5.5%] versus 1.2% [5.7%], P=0.007), but by 18 months the response in both groups trend toward baseline (-1.1% [5.8%] versus 0.2% [4.8%], P=0.3). Low-density lipoprotein cholesterol was not associated with changes in augmentation index at any time point. Conclusions Statin therapy led to a short-term reduction in augmentation index after 12 months, but this effect did not persist after 18 months despite continued reduction in low-density lipoprotein cholesterol levels. These findings suggest that statins may have a transient effect on aortic stiffness. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00939822.
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Effects of regular high-cocoa chocolate intake on arterial stiffness and metabolic characteristics during exercise.
Nishiwaki, M, Nakano, Y, Matsumoto, N
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:53-58
Abstract
OBJECTIVE The aim of this study was to examine the effects of regular high-cocoa chocolate consumption on arterial stiffness and fat oxidation during light- to moderate-intensity exercise. METHODS This randomized, controlled, parallel-group intervention study included 32 Japanese college students (mean age, 20.7 ± 0.3 y; men, n = 24; women, n = 8) who were assigned to either control or intervention groups (n = 16 each). The control group did not alter their habitual diet or physical activity throughout the study period. The intervention group consumed 20 g/d (508 mg of cacao polyphenol) of high-cocoa chocolate for 4 wk. Blood pressure, heart-ankle pulse wave velocity, cardio-ankle vascular index, body composition, and metabolic characteristics during exercise at 50% maximal oxygen uptake level were assessed before and after the intervention. RESULTS Four weeks of high-cocoa chocolate ingestion significantly reduced heart-ankle pulse wave velocity and cardio-ankle vascular index (%change, intervention versus control: -2.3 ± 0.9% versus 0.9 ± 0.9%, and -4.8 ± 1.8% versus 0.7 ± 1.3%, respectively; both P < 0.05). However, blood pressure, weight, body mass index, body fat, waist circumference, and metabolic characteristics during exercise such as respiratory exchange ratio did not significantly change in either group. CONCLUSIONS Four weeks of regular high-cocoa chocolate consumption reduced arterial stiffness after considering blood pressure in healthy young men and women. However, the habitual consumption of high-cocoa chocolate for 4 wk did not affect metabolic characteristics during light- to moderate-intensity exercise and body composition.
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Association of Cardiovascular Autonomic Dysfunction With Peripheral Arterial Stiffness in Patients With Type 1 Diabetes.
Nattero-Chávez, L, Redondo López, S, Alonso Díaz, S, Garnica Ureña, M, Fernández-Durán, E, Escobar-Morreale, HF, Luque-Ramírez, M
The Journal of clinical endocrinology and metabolism. 2019;(7):2675-2684
Abstract
CONTEXT Cardiovascular autonomic neuropathy (CAN) appears to contribute to peripheral arterial stiffness (AS) in type 1 diabetes. Whether CAN in patients with AS is associated with concomitant asymptomatic peripheral arterial disease (aPAD) remains unclear. OBJECTIVE To assess the risk of CAN in patients with type 1 diabetes and AS and its potential association with atherosclerosis. DESIGN Cross-sectional study. SETTING Type 1 diabetes clinic in an academic hospital. PATIENTS Two hundred sixty-four patients with type 1 diabetes. INTERVENTION AS was defined as an ankle-brachial index (ABI) >1.2, aPAD by the toe-brachial index and Doppler sonography, and CAN by blood pressure and heart rate responses to active standing and Ewing and Clarke tests. MAIN OUTCOME MEASURES Odds of having CAN among patients with AS. Odds for CAN were also calculated as a function of the presence of AS and concomitant aPAD. RESULTS The study population's mean age was 35 ± 11 years, with a duration of disease of 19 ± 10 years and mean hemoglobin A1c of 7.5% ± 1.3%. Seventy-three patients (28%) had peripheral AS, of whom 28 showed aPAD. The prevalence of CAN among patients with AS was 48% but it was only 23% in subjects with normal ABI (OR: 3.1 [1.7; 5.4]). Concomitant aPAD increased the OR for CAN (OR: 4.5 [2.0; 10.1]). After adjustments for aPAD and relevant cardiovascular risk factors, AS remained associated with parasympathetic dysfunction. CONCLUSIONS In type 1 diabetes, both peripheral AS and atherosclerosis were associated with CAN. A simple method, such as the ABI, may identify a subset of patients with undiagnosed dysautonomia.
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Switching Dipeptidyl Peptidase-4 Inhibitors to Tofogliflozin, a Selective Inhibitor of Sodium-Glucose Cotransporter 2 Improve Arterial Stiffness Evaluated by Cardio-Ankle Vascular Index in Patients with Type 2 Diabetes: A Pilot Study.
Bekki, M, Tahara, N, Tahara, A, Igata, S, Honda, A, Sugiyama, Y, Nakamura, T, Sun, J, Kumashiro, Y, Matsui, T, et al
Current vascular pharmacology. 2019;(4):411-420
Abstract
BACKGROUND We have found that anagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4) significantly ameliorates arterial stiffness in Type 2 Diabetes Mellitus (T2DM) patients compared with an equivalent hypoglycaemic agent, glimepiride. However, it remains unclear whether switching DPP-4 inhibitors to tofogliflozin, a selective inhibitor of Sodium-Glucose Cotransporter 2 (SGLT2) improves arterial stiffness in T2DM patients. METHODS Nineteen T2DM patients who had received DPP-4 inhibitors for at least 1 year were enrolled in this study. Clinical parameters and arterial stiffness evaluated by cardio-ankle vascular index (CAVI) were measured at baseline and after 6-months treatment with tofogliflozin. RESULTS At 6 months after switching to tofogliflozin, CAVI, waist circumference, body weight, body mass index, subcutaneous and visceral fat volume, white blood cell number, fasting plasma insulin, uric acid, aspartate transaminase (AST), γ-glutamyl transferase (GTP), and advanced glycation end products (AGEs) were significantly reduced, while red blood cell number, haemoglobin, and HbA1c values were increased. When stratified by median values of change in CAVI after switching to tofogliflozin (ΔCAVI), baseline serum levels of AGEs were significantly higher in the low ΔCAVI group (high responder) than in the high one (low responder). ΔAST and ΔGTP were positively correlated with ΔCAVI. CONCLUSION The present study suggests that switching DPP-4 inhibitors to tofogliflozin ameliorates arterial stiffness in T2DM patients partly via improvement of liver function. Baseline serum levels of AGEs may identify patients who improve arterial stiffness more after treatment with tofogliflozin.