-
1.
Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD: A Randomized Controlled Trial.
Nowak, KL, Farmer-Bailey, H, Wang, W, You, Z, Steele, C, Cadnapaphornchai, MA, Klawitter, J, Patel, N, George, D, Jovanovich, A, et al
Clinical journal of the American Society of Nephrology : CJASN. 2022;(2):240-250
-
-
Free full text
-
Abstract
BACKGROUND AND OBJECTIVES Clinical manifestations of autosomal dominant polycystic kidney disease (ADPKD), including evidence of vascular dysfunction, can begin in childhood. Curcumin is a polyphenol found in turmeric that reduces vascular dysfunction in rodent models and humans without ADPKD. It also slows kidney cystic progression in a murine model of ADPKD. We hypothesized that oral curcumin therapy would reduce vascular endothelial dysfunction and arterial stiffness in children/young adults with ADPKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In a randomized, placebo-controlled, double-blind trial, 68 children/young adults 6-25 years of age with ADPKD and eGFR>80 ml/min per 1.73 m2 were randomized to either curcumin supplementation (25 mg/kg body weight per day) or placebo administered in powder form for 12 months. The coprimary outcomes were brachial artery flow-mediated dilation and aortic pulse-wave velocity. We also assessed change in circulating/urine biomarkers of oxidative stress/inflammation and kidney growth (height-adjusted total kidney volume) by magnetic resonance imaging. In a subgroup of participants ≥18 years, vascular oxidative stress was measured as the change in brachial artery flow-mediated dilation following an acute infusion of ascorbic acid. RESULTS Enrolled participants were 18±5 (mean ± SD) years, 54% were girls, baseline brachial artery flow-mediated dilation was 9.3±4.1% change, and baseline aortic pulse-wave velocity was 512±94 cm/s. Fifty-seven participants completed the trial. Neither coprimary end point changed with curcumin (estimated change [95% confidence interval] for brachial artery flow-mediated dilation [percentage change]: curcumin: 1.14; 95% confidence interval, -0.84 to 3.13; placebo: 0.33; 95% confidence interval, -1.34 to 2.00; estimated difference for change: 0.81; 95% confidence interval, -1.21 to 2.84; P=0.48; aortic pulse-wave velocity [centimeters per second]: curcumin: 0.6; 95% confidence interval, -25.7 to 26.9; placebo: 6.5; 95% confidence interval, -20.4 to 33.5; estimated difference for change: -5.9; 95% confidence interval, -35.8 to 24.0; P=0.67; intent to treat). There was no curcumin-specific reduction in vascular oxidative stress or changes in mechanistic biomarkers. Height-adjusted total kidney volume also did not change as compared with placebo. CONCLUSIONS Curcumin supplementation does not improve vascular function or slow kidney growth in children/young adults with ADPKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD, NCT02494141. PODCAST This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_02_07_CJN08950621.mp3.
-
2.
Microcirculation and Macrocirculation in Hypertension: A Dangerous Cross-Link?
Laurent, S, Agabiti-Rosei, C, Bruno, RM, Rizzoni, D
Hypertension (Dallas, Tex. : 1979). 2022;(3):479-490
Abstract
Microcirculation and macrocirculation are tightly interconnected into a dangerous cross-link in hypertension. Small artery damage includes functional (vasoconstriction, impaired vasodilatation) and structural abnormalities (mostly inward eutrophic remodeling). These abnormalities are major determinants of the increase in total peripheral resistance and mean blood pressure (BP) in primary hypertension, which in the long term induces large artery stiffening. In turn, large artery stiffening increases central systolic and pulse pressures, which are further augmented by wave reflection in response to the structural alterations in small resistance arteries. Finally, transmission of high BP and flow pulsatility to small resistance arteries further induces functional and structural abnormalities, thus leading to increased total peripheral resistance and mean BP, thus perpetuating the vicious circle. Hyperpulsatility, in addition to higher mean BP, exaggerates cardiac, brain, and kidney damages and leads to cardiovascular, cerebral, and renal complications. The dangerous cross-link between micro and macrocirculation can be reversed into a virtuous one by ACE (angiotensin-converting enzyme) inhibitors, sartans, and calcium channel blockers. These three pharmacological classes are more potent than β-blockers and diuretics for reducing arterial stiffness and small artery remodeling. The same ranking was observed for their effectiveness at reducing left ventricular hypertrophy, preserving glomerular filtration rate, and preventing dementia, suggesting that they can act beyond brachial BP reduction, by breaking the micro/macrocirculation vicious circle.
-
3.
Vitamin K2-a neglected player in cardiovascular health: a narrative review.
Hariri, E, Kassis, N, Iskandar, JP, Schurgers, LJ, Saad, A, Abdelfattah, O, Bansal, A, Isogai, T, Harb, SC, Kapadia, S
Open heart. 2021;(2)
Abstract
Vitamin K2 serves an important role in cardiovascular health through regulation of calcium homeostasis. Its effects on the cardiovascular system are mediated through activation of the anti-calcific protein known as matrix Gla protein. In its inactive form, this protein is associated with various markers of cardiovascular disease including increased arterial stiffness, vascular and valvular calcification, insulin resistance and heart failure indices which ultimately increase cardiovascular mortality. Supplementation of vitamin K2 has been strongly associated with improved cardiovascular outcomes through its modification of systemic calcification and arterial stiffness. Although its direct effects on delaying the progression of vascular and valvular calcification is currently the subject of multiple randomised clinical trials, prior reports suggest potential improved survival among cardiac patients with vitamin K2 supplementation. Strengthened by its affordability and Food and Drug Adminstration (FDA)-proven safety, vitamin K2 supplementation is a viable and promising option to improve cardiovascular outcomes.
-
4.
Cytomegalovirus infection is associated with an increase in aortic stiffness in older men which may be mediated in part by CD4 memory T-cells.
Kirkham, F, Pera, A, Simanek, AM, Bano, A, Morrow, G, Reus, B, Caserta, S, Smith, HE, Davies, KA, Rajkumar, C, et al
Theranostics. 2021;(12):5728-5741
Abstract
Human Cytomegalovirus (CMV) infection is associated with atherosclerosis, higher cardiovascular disease (CVD) risk, and an increase in memory T-cells (Tmem). T-cells have also been implicated in CVD, independently of CMV infection. To better understand the CMV-associated CVD risk, we examined the association between CMV (IgG) serostatus and central aortic (carotid-to-femoral) pulse wave velocity (cfPWV), an early, independent predictor of CVD. We also investigated if such an association might be reflected by the distribution of Tmem and/or other T-cell subsets. Methods: Healthy older volunteers (60-93 years) underwent routine clinical and laboratory evaluation, including assessment of cfPWV in eligible participants. Flow-cytometry was used to assess proportions of memory T-cells, CD28null T-cells, and CMV-specific T-cells. The following associations were examined; CMV serostatus/cfPWV, CMV serostatus/proportion of Tmem, proportion of Tmem/cfPWV, CD28null T-cells/cfPWV, and CMV-specific T-cells/cfPWV. Linear regression models were used to adjust for age, sex, socioeconomic status, smoking, waist-to-hip ratio, cholesterol, and blood pressure as required. Results: Statistically significant positive associations were found (P-values for the fully adjusted models are given); CMV serostatus/cfPWV in men (P ≤ 0.01) but not in women, CMV serostatus/proportions of CD4 Tmem in men (P ≤ 0.05) but not in women; proportions of CD4 Tmem/cfPWV among CMV seropositive (CMV+) people (P ≤ 0.05) but not CMV seronegative (CMV-) people. Conclusion: CMV infection increases the CVD risk of older men by increasing cfPWV. This may be mediated in part by increased proportions of CD4 Tmem, higher numbers of which are found in CMV+ older people and more so among men than women. Given the high prevalence of CMV worldwide, our findings point to a significant global health issue. Novel strategies to mitigate the increased CVD risk associated with CMV may be required.
-
5.
A Low-Calorie Diet with or without Exercise Reduces Postprandial Aortic Waveform in Females with Obesity.
Heiston, EM, Gilbertson, NM, Eichner, NZM, Malin, SK
Medicine and science in sports and exercise. 2021;(4):796-803
Abstract
PURPOSE Arterial stiffness is considered a predictor of cardiovascular disease. Females have higher values of arterial stiffness than males, suggesting a greater risk of heart-related complications. Although a low-calorie diet (LCD) reduces fasting arterial stiffness, in part through weight loss, it is unknown if interval exercise (INT) adds to the benefit of LCD on fasting and postprandial arterial stiffness in females with obesity. METHODS Twenty-five females (47 ± 2.6 yr, 37.6 ± 1.3 kg·m-2) were randomized to 13 d of LCD (n = 12; mixed meals of ~1200 kcal·d-1) or LCD + INT (n = 13; 60 min·d-1 of supervised 3-min intervals at 90% HRpeak and 50% HRpeak). Arterial stiffness (augmentation index [AIx] and carotid-femoral pulse wave velocity [cfPWV]) and blood biochemistries were measured during a 75-g oral glucose tolerance test before and after the intervention to determine fasting and postprandial arterial stiffness as well as insulin sensitivity (simple index of insulin sensitivity [SIIS]) and inflammation (C-reactive protein, interleukin 8, and tumor necrosis factor alpha). RESULTS Although LCD + INT increased V˙O2peak and HDL compared with LCD (P = 0.04 and P < 0.01, respectively), both interventions decreased body fat, LDL, total cholesterol, and triglycerides (all P < 0.01) and increased SIIS (P = 0.03). Despite no effect on fasting AIx (P = 0.27), LCD and LCD + INT decreased AIx60min (-7.4% ± 4.3% vs -7.0% ± 5.0%, P = 0.04) and tAUC120min (-663 ± 263 vs -457 ± 406, P = 0.03). There were no changes in fasting cfPWV (P = 0.91) or cfPWV120min (P = 0.62). Increased SIIS and decreased interleukin 8 were associated with reduced fasting AIx (r = -0.44, P = 0.03, and r = 0.40, P = 0.055), whereas decreased C-reactive protein correlated with reduced postprandial AIx60min (r = 0.43, P = 0.04). CONCLUSION Independent of exercise, 13 d of LCD reduces postprandial AIx in females with obesity. Insulin sensitivity and inflammation correlated with improved arterial stiffness, suggesting unique mechanisms regulate fasted versus postprandial arterial stiffness.
-
6.
Effect of sotagliflozin as an adjunct to insulin therapy on blood pressure and arterial stiffness in adults with type 1 diabetes: A post hoc pooled analysis of inTandem1 and inTandem2.
Rodbard, HW, Giaccari, A, Cariou, B, Garg, S, Davies, MJ, Seth, K, Sawhney, S
Diabetes & vascular disease research. 2021;(1):1479164121995928
Abstract
OBJECTIVE Evaluate the effect of sotagliflozin, a dual inhibitor of sodium glucose cotransporter (SGLT) 1 and 2, on arterial stiffness in patients with type 1 diabetes (T1D) treated with sotagliflozin as adjunct to optimized insulin therapy. METHODS In this post hoc analysis, indirect markers of arterial stiffness, including pulse pressure, mean arterial pressure (MAP), and double product, were calculated using observed systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse rate at 24 weeks using data from a pooled patient population from the inTandem1 and inTandem2 randomized controlled trials (n = 1575). RESULTS Baseline characteristics were similar among groups. Relative to placebo at Week 24, sotagliflozin 200 mg and 400 mg reduced SBP by 2.03 mm Hg (95% CI -3.30 to -0.75; p = 0.0019) and 2.85 mm Hg (-4.12 to -1.57; p < 0.0001), respectively. DBP decreased by 1.1 and 0.9 mm Hg, MAP by 1.4 and 1.6 mm Hg, and double product by 202.5 and 221.1 bpm × mm Hg, respectively (p < 0.05 for all). No increases in heart rate were observed. CONCLUSION In adults with T1D, adding sotagliflozin to insulin significantly reduced blood pressure and other markers of arterial stiffness and vascular resistance.
-
7.
Effect of tofogliflozin on arterial stiffness in patients with type 2 diabetes: prespecified sub-analysis of the prospective, randomized, open-label, parallel-group comparative UTOPIA trial.
Katakami, N, Mita, T, Yoshii, H, Shiraiwa, T, Yasuda, T, Okada, Y, Torimoto, K, Umayahara, Y, Kaneto, H, Osonoi, T, et al
Cardiovascular diabetology. 2021;(1):4
Abstract
BACKGROUND Tofogliflozin, an SGLT2 inhibitor, is associated with favorable metabolic effects, including improved glycemic control and serum lipid profile and decreased body weight, visceral adipose tissue, and blood pressure (BP). This study evaluated the effects of tofogliflozin on the brachial-ankle pulse wave velocity (baPWV) in patients with type 2 diabetes (T2DM) without a history of apparent cardiovascular disease. METHODS The using tofogliflozin for possible better intervention against atherosclerosis for type 2 diabetes patients (UTOPIA) trial is a prospective, randomized, open-label, multicenter, parallel-group, comparative study. As one of the prespecified secondary outcomes, changes in baPWV over 104 weeks were evaluated in 154 individuals (80 in the tofogliflozin group and 74 in the conventional treatment group) who completed baPWV measurement at baseline. RESULTS In a mixed-effects model, the progression in the right, left, and mean baPWV over 104 weeks was significantly attenuated with tofogliflozin compared to that with conventional treatment (- 109.3 [- 184.3, - 34.3] (mean change [95% CI] cm/s, p = 0.005; - 98.3 [- 172.6, - 24.1] cm/s, p = 0.010; - 104.7 [- 177.0, - 32.4] cm/s, p = 0.005, respectively). Similar findings were obtained even after adjusting the mixed-effects models for traditional cardiovascular risk factors, including body mass index (BMI), glycated hemoglobin (HbA1c), total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, systolic blood pressure (SBP), hypertension, smoking, and/or administration of drugs, including hypoglycemic agents, antihypertensive agents, statins, and anti-platelets, at baseline. The findings of the analysis of covariance (ANCOVA) models, which included the treatment group, baseline baPWV, and traditional cardiovascular risk factors, resembled those generated by the mixed-effects models. CONCLUSIONS Tofogliflozin significantly inhibited the increased baPWV in patients with T2DM without a history of apparent cardiovascular disease, suggesting that tofogliflozin suppressed the progression of arterial stiffness. Trial Registration UMIN000017607. Registered 18 May 2015. ( https://www.umin.ac.jp/icdr/index.html ).
-
8.
The acute effects of vinyasa flow yoga on vascular function, lipid and glucose concentrations, and mood.
Piña, AA, Shadiow, J, Tobi Fadeyi, A, Chavez, A, Hunter, SD
Complementary therapies in medicine. 2021;:102585
Abstract
While the chronic effects of certain styles of yoga on cardiometabolic factors have been investigated, little is known about the acute effects of a single yoga session on these outcomes. Moreover, vinyasa yoga's potential to modulate cardiometabolic outcomes has not been established. The purpose of this study is to determine the acute effects of a vinyasa yoga session on arterial stiffness, wave reflection, lipid and glucose concentrations, and mood in adults with prior yoga experience. Thirty yoga practitioners with a minimum of 3 months of practice experience were enrolled into the study. Carotid-femoral pulse wave velocity (cf-PWV), augmentation index (AIx), lipid profile, glucose concentrations, and mood (Positive and Negative Affect Scale) were assessed at baseline and immediately following a 1 -h vinyasa yoga session. After the yoga session, participants had significantly lower AIx (p < 0.001), non-HDL cholesterol (p < 0.05), and negative affect (p < 0.01) compared to baseline. These results highlight the efficacy of a single bout of yoga in altering wave reflection while improving mood and lipid concentrations in healthy adults with a history of yoga practice.
-
9.
The Effect of Aerobic Exercise Training Frequency on Arterial Stiffness in a Hyperglycemic State in Middle-Aged and Elderly Females.
Kobayashi, R, Asaki, K, Hashiguchi, T, Negoro, H
Nutrients. 2021;(10)
Abstract
The frequency of aerobic exercise training in reducing the increase in arterial stiffness during acute hyperglycemia, a risk factor for cardiovascular disease, is unknown. The aim of the study was to determine the aerobic exercise training frequency on arterial stiffness in a hyperglycemic state in middle-aged and elderly females. Twenty healthy elderly people were randomly assigned to a two-times-a-week (T2, n = 10) and four-times-a-week (T4, n = 10) exercise group. All participants exercised for 35 min per session, which consisted of jogging exercises with a heart rate intensity of 65%. Brachial-ankle (ba), and heart-brachial (hb) pulse wave velocity (PWV) were measured before, 4 and 8 weeks after intervention; before the oral ingestion of 75-g of glucose; and 30, 60, and 90 min after ingestion. The baPWV before and 4 weeks after the intervention increased in both groups (p < 0.05), but only increased 8 weeks after intervention in the T2 group. hbPWV was unchanged before, 4 and 8 weeks after intervention in both groups. These findings show that frequent aerobic exercise suppresses the increase in arterial stiffness following glucose intake. The results of this study can be used to support the implementation of exercise programs for middle-aged and elderly patients.
-
10.
Effects of Different Types of Carbohydrates on Arterial Stiffness: A Comparison of Isomaltulose and Sucrose.
Kobayashi, R, Sakazaki, M, Nagai, Y, Asaki, K, Hashiguchi, T, Negoro, H
Nutrients. 2021;(12)
Abstract
Increased arterial stiffness during acute hyperglycemia is a risk factor for cardiovascular disease, but the type of carbohydrate that inhibits it is unknown. The purpose of this study was to determine the efficacy of low-glycemic-index isomaltulose on arterial stiffness during hyperglycemia in middle-aged and older adults. Ten healthy middle-aged and older adult subjects orally ingested a solution containing 25 g of isomaltulose (ISI trial) and sucrose (SSI trial) in a crossover study. In the SSI trial, the brachial-ankle (ba) pulse wave velocity (PWV) increased 30, 60, and 90 min after ingestion compared with that before ingestion (p < 0.01); however, in the ISI trial, the baPWV did not change after ingestion compared with that before ingestion. Blood glucose levels 30 min after intake were lower in the ISI trial than in the SSI trial (p < 0.01). The baPWV and systolic blood pressure were positively correlated 90 min after isomaltulose and sucrose ingestion (r = 0.640, p < 0.05). These results indicate that isomaltulose intake inhibits an acute increase in arterial stiffness. The results of the present study may have significant clinical implications on the implementation of dietary programs for middle-aged and elderly patients.