The Prospective Studies of Atherosclerosis (Proof-ATHERO) Consortium: Design and Rationale.

Atherosclerosis - the pathophysiological mechanism shared by most cardiovascular diseases - can be directly or indirectly assessed by a variety of clinical tests including measurement of carotid intima-media thickness, carotid plaque, -ankle-brachial index, pulse wave velocity, and coronary -artery calcium. The Prospective Studies of Atherosclerosis -(Proof-ATHERO) consortium (https://clinicalepi.i-med.ac.at/research/proof-athero/) collates de-identified individual-participant data of studies with information on atherosclerosis measures, risk factors for cardiovascular disease, and incidence of cardiovascular diseases. It currently comprises 74 studies that involve 106,846 participants from 25 countries and over 40 cities. In summary, 21 studies recruited participants from the general population (n = 67,784), 16 from high-risk populations (n = 22,677), and 37 as part of clinical trials (n = 16,385). Baseline years of contributing studies range from April 1980 to July 2014; the latest follow-up was until June 2019. Mean age at baseline was 59 years (standard deviation: 10) and 50% were female. Over a total of 830,619 person-years of follow-up, 17,270 incident cardiovascular events (including coronary heart disease and stroke) and 13,270 deaths were recorded, corresponding to cumulative incidences of 2.1% and 1.6% per annum, respectively. The consortium is coordinated by the Clinical Epidemiology Team at the Medical University of Innsbruck, Austria. Contributing studies undergo a detailed data cleaning and harmonisation procedure before being incorporated in the Proof-ATHERO central database. Statistical analyses are being conducted according to pre-defined analysis plans and use established methods for individual-participant data meta-analysis. Capitalising on its large sample size, the multi-institutional collaborative Proof-ATHERO consortium aims to better characterise, understand, and predict the development of atherosclerosis and its clinical consequences.

May Measurement Month 2018: an analysis of blood pressure screening results from Brazil.

Hypertension is a pathology of high prevalence in the world. In Brazil, it is the main risk factor for the major cause of death in the country, coronary heart disease. The May Measurement Month Campaign in 2018 (MMM18) included a population with representation from all Brazilian states and reflects some of the characteristics of hypertension in Brazil. Questionnaire data were collected and three measures of blood pressure (BP) were performed. The sample consisted of 12 413 individuals, 59.1% were white, 51.3% were women. The average age was 54. ± 16.0 years. Diabetes was present in 11.6%, previous myocardial infarction in 5.9%, and previous stroke in 2.7%. Current smokers were 9.3% and 12.4% were regular drinkers. The average body mass index was 27.3 ± 4.5 kg/m2. After multiple imputations, 67.9% were hypertensive (>140/90 mmHg). Of the individuals who were not taking antihypertensive medication, 27.9% were hypertensive and of those taking antihypertensive medication, 40.3% were uncontrolled. Systolic BP increased with age. The MMM18 campaign demonstrated a large number of unknown hypertensives and a high rate of uncontrolled hypertension in Brazil, unfortunately in keeping with 2017 findings.

Acute Effect of Aerobic and Strength Exercise on Heart Rate Variability and Baroreflex Sensitivity in Men With Autonomic Dysfunction.

de Paula, T, Neves, MF, da Silva Itaborahy, A, Monteiro, W, Farinatti, P, and Cunha, FA. Recovery pattern of cardiac autonomic control after aerobic and strength exercises in overweight prehypertensive men. J Strength Cond Res 33(10): 2743-2752, 2019-The extent to which postexercise cardiac autonomic control depends on exercise modality remains unclear, particularly among individuals with autonomic dysfunction (cardiac autonomic dysfunction [CADysf]). This study compared heart rate variability (HRV) and baroreflex sensitivity (BRS) responses to acute aerobic exercise (AE) and strength exercise (SE) in men with CADysf. Twenty men were assigned into control (n = 10: 33.8 ± 3.0 years; 23.7 ± 1.5 kg·m) and CADysf (n = 10: 36.2 ± 9.8 years; 28.4 ± 2.6 kg·m) groups. Cardiac autonomic dysfunction underwent AE, SE, and a nonexercise control day (control session [CTL]) in a randomized, counter-balanced order. Heart rate variability and BRS were assessed in a supine position during 25 minutes of recovery after AE, SE, and CTL. Both HRV indices (p ≤ 0.05; effect size [Cohen's d]: >1.4) and BRS at rest were significantly lower in CADysf than those in controls (p < 0.01; effect size [Cohen's d]: ≥1.36). In CADysf, postexercise increases in heart rate, sympathetic activity (low-frequency [LF] band), and sympathovagal balance (LF:high-frequency [HF] ratio), as well as decreases in R-R interval, parasympathetic activity (HF band), and BRS were observed in AE (p ≤ 0.05; effect size [Cohen's d]: ≥1.31) and SE (p ≤ 0.05; effect size [Cohen's d]: ≥0.79) vs. CTL, but changes were larger after AE than SE (p ≤ 0.05; effect size [Cohen's d]: ≥0.73). In conclusion, both AE and SE elicited postexercise changes in HRV and BRS among CADysf men, primarily reflected by lowered vagal modulation, increased sympathovagal balance, and a delayed BRS recovery pattern. However, those changes seem to be more likely to occur after AE than SE.

Insulin reference intervals in Brazilian adolescents by direct and indirect approaches: validation of a data mining method from laboratory data.

OBJECTIVE: To determine reference intervals (RI) for fasting blood insulin (FBI) in Brazilian adolescents, 12 to 17 years old, by direct and indirect approaches, and to validate indirectly determined RI. METHODS: Two databases were used for RI determination. Database 1 (DB1), used to obtain RI through a posteriori direct method, consisted of prospectively selected healthy individuals. Database 2 (DB2) was retrospectively mined from an outpatient laboratory information system (LIS) used for the indirect method (Bhattacharya method). RESULTS: From DB1, 29345 individuals were enrolled (57.65 % female) and seven age ranges and sex partitions were statistically determined according to mean FBI values: females: 12 and 13 years-old, 14 years-old, 15 years-old, 16 and 17 years-old; and males: 12, 13 and 14 years-old, 15 years-old, 16 and 17 years-old. From DB2, 5465 adolescents (67.5 % female) were selected and grouped according to DB1 partitions. The mean FBI level was significantly higher in DB2, on all groups. The RI upper limit (URL) determined by Bhattacharya method was slightly lower than the 90 % CI URL directly obtained on DB1, except for group female 12 and 13 years old. High agreement rates for diagnosing elevated FBI in all groups on DB1 validated indirect RI presented. CONCLUSION: The present study demonstrates that Bhattacharya indirect method to determine FBI RI in adolescents can overcome some of the difficulties and challenges of the direct approach.

Arterial Stiffness Associated with Sympathetic Hyperactivity in Obese Individuals with Moderate to Severe Obstructive Sleep Apnea.

INTRODUCTION: Obstructive Sleep Apnea (OSA) is a chronic disorder associated with several risk factors, and increased Body Mass Index (BMI) and waist circumference are correlated with it is severity. AIM: To evaluate vascular function, central hemodynamics, and autonomic modulation in obese individuals with moderate and severe OSA. METHODS: Individuals of both sexes, aged 40-70 years and BMI ≥ 30 and < 40 kg/m2, were submitted to assessment of heart rate variability, endothelial function by flow-mediated dilatation, central parameters by oscillometry and carotid ultrasound. The sleep study was performed through a portable home sleep test device (WatchPAT). RESULTS: Patients (n = 76) were divided according to Apnea-Hypopnea Index (AHI): absent-mild group (AHI < 15 events/h, n = 30) and Moderate-Severe (MS) group (AHI ≥ 15 events/h, n = 46). The Low/High Frequency (LF/HF) ratio (0.81 ± 0.48 vs 1.39 ± 1.08 ms2, p = 0.035), Pulse Wave Velocity (PWV; 6.9 ± 0.7 vs 7.7 ± 1.6m/s, p = 0.004), vascular age (48 ± 6 vs 53 ± 9 years, p = 0.05) and mean intima-media thickness (0.59 ± 0.08 vs 0.66 ± 0.13 mm, p = 0.011) were significantly higher in the MS group. AHI was significantly correlated with PWV (r = 0.26, p = 0.024) and LF/HF ratio (r = 0.40, p < 0.001). Only in the MS group, PWV was significantly correlated with SD2/SD1 ratio (r = 0.611, p ≤ 0.001), and flow-mediated dilation with central systolic blood pressure (r = 0.364, p = 0.018), even after adjustment for age and sex. CONCLUSION: In this sample of obese individuals, moderate to severe OSA was associated with sympathetic hyperactivity and evidence of accelerated vascular aging with arterial stiffness and subclinical atherosclerosis.

Effects of aerobic, resistance and concurrent exercise on pulse wave reflection and autonomic modulation in men with elevated blood pressure.

The acute effects of exercise modes on pulse wave reflection (PWR) and their relationship with autonomic control remain undefined, particularly in individuals with elevated blood pressure (BP). We compared PWR and autonomic modulation after acute aerobic (AE), resistance (RE), and concurrent exercise (CE) in 15 men with stage-1 hypertension (mean ± SE: 34.7 ± 2.5 years, 28.4 ± 0.6 kg/m2, 133 ± 1/82 ± 2 mmHg). Participants underwent AE, RE, and CE on different days in counterbalanced order. Applanation tonometry and heart rate variability assessments were performed before and 30-min postexercise. Aortic pressure decreased after AE (- 2.4 ± 0.7 mmHg; P = 0.01), RE (- 2.2 ± 0.6 mmHg; P = 0.03), and CE (- 3.1 ± 0.5 mmHg; P = 0.003). Augmentation index remained stable after RE, but lowered after AE (- 5.1 ± 1.7%; P = 0.03) and CE (- 7.6 ± 2.4% P = 0.002). Systolic BP reduction occurred after CE (- 5.3 ± 1.9 mmHg). RR-intervals and parasympathetic modulation lowered after all conditions (~ 30-40%; P < 0.05), while the sympathovagal balance increased after RE (1.2 ± 0.3-1.3 ± 0.3 n.u., P < 0.05). Changes in PWR correlated inversely with sympathetic and directly with vagal modulation in CE. In conclusion, AE, RE, and CE lowered central aortic pressure, but only AE and CE reduced PWR. Overall, those reductions related to decreased parasympathetic and increased sympathetic outflows. Autonomic fluctuations seemed to represent more a consequence than a cause of reduced PWR.

Endothelium-restricted endothelin-1 overexpression in type 1 diabetes worsens atherosclerosis and immune cell infiltration via NOX1.

AIMS: NADPH oxidase (NOX) 1 but not NOX4-dependent oxidative stress plays a role in diabetic vascular disease, including atherosclerosis. Endothelin (ET)-1 has been implicated in diabetes-induced vascular complications. We showed that crossing mice overexpressing human ET-1 selectively in endothelium (eET-1) with apolipoprotein E knockout (Apoe-/-) mice enhanced high-fat diet-induced atherosclerosis in part by increasing oxidative stress. We tested the hypothesis that ET-1 overexpression in the endothelium would worsen atherosclerosis in type 1 diabetes through a mechanism involving NOX1 but not NOX4. METHODS AND RESULTS: Six-week-old male Apoe-/- and eET-1/Apoe-/- mice with or without Nox1 (Nox1-/y) or Nox4 knockout (Nox4-/-) were injected intraperitoneally with either vehicle or streptozotocin (55 mg/kg/day) for 5 days to induce type 1 diabetes and were studied 14 weeks later. ET-1 overexpression increased 2.5-fold and five-fold the atherosclerotic lesion area in the aortic sinus and arch of diabetic Apoe-/- mice, respectively. Deletion of Nox1 reduced aortic arch plaque size by 60%; in contrast, Nox4 knockout increased lesion size by 1.5-fold. ET-1 overexpression decreased aortic sinus and arch plaque alpha smooth muscle cell content by ∼35% and ∼50%, respectively, which was blunted by Nox1 but not Nox4 knockout. Reactive oxygen species production was increased two-fold in aortic arch perivascular fat of diabetic eET-1/Apoe-/- and eET-1/Apoe-/-/Nox4-/- mice but not eET-1/Apoe-/-/Nox1y/- mice. ET-1 overexpression enhanced monocyte/macrophage and CD3+ T-cell infiltration ∼2.7-fold in the aortic arch perivascular fat of diabetic Apoe-/- mice. Both Nox1 and Nox4 knockout blunted CD3+ T-cell infiltration whereas only Nox1 knockout prevented the monocyte/macrophage infiltration in diabetic eET-1/Apoe-/- mice. CONCLUSION: Endothelium ET-1 overexpression enhances the progression of atherosclerosis in type 1 diabetes, perivascular oxidative stress, and inflammation through NOX1.

Effects of Whole-Body Vibration in Older Adult Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

OBJECTIVES: The aim of this systematic review and meta-analysis was to determine the effects of whole-body vibration training on metabolic abnormalities, mobility, balance and aerobic capacity in older adult patients with type 2 diabetes mellitus. METHODS: We searched PubMed, Cochrane Library, PEDro, LILACS and SciELO (from the earliest date available to March 2018) for controlled trials that evaluated the effects of whole-body vibration on the health-related outcomes of patients with type 2 diabetes. Two reviewers independently selected the studies and performed statistical analyses of the studies. Weighted mean differences, standard mean differences and 95% confidence intervals (CIs) were calculated. RESULTS: In total, 7 studies, involving 279 patients who had type 2 diabetes, that compared whole-body vibration with other exercises and/or controls were included. Individual studies suggested that whole-body vibration was associated with improvements in pain levels, blood flow in the legs, glycated hemoglobin levels and fasting blood glucose levels. Whole-body vibration improved mobility weighted mean differences (-.24 seg; 95% CI -2.0, -0.5; n=96); balance standard mean differences (2.34; 95% CI 1.16, 3.5; n=57); and aerobic capacity standard mean differences (0.7; 95% CI 0.2, 1.3; n=59). CONCLUSIONS: Whole-body vibration could be a useful strategy in the management of the symptoms and disabilities associated with type 2 diabetes; however, it is necessary to perform further studies to reinforce the reported findings.

Association of urinary sodium/potassium ratio with structural and functional vascular changes in non-diabetic hypertensive patients.

Studies aiming to associate the sodium/potassium (Na/K) ratio with hypertension use 24-hour urinary excretion as a daily marker of ingestion. The objective of this study was to evaluate the association between urinary Na/K ratio and structural and functional vascular alterations in non-diabetic hypertensive patients. In hypertensive patients (n = 72), aged between 40 and 70 years, both sexes (61% women), in use of hydrochlorothiazide, we measured blood pressure, 24-hour urine sample collection, assessment of carotid-femoral pulse wave velocity (cf-PWV, Complior), central hemodynamic parameters (SphygmoCor), and post-occlusive reactive hyperemia (PORH). The participants were divided according to the tertile of 24-hour urinary Na/K ratio. Each group contained 24 patients. Systolic blood pressure was higher in T2 (133 ± 9 vs 140 ± 9 mmHg, P = .029). C-reactive protein (CRP) presented higher values in T3 as compared to T1 [0.20(0.10-0.34) vs 1.19 (0.96-1.42) mg/dL, P < .001]. Higher values in T3 were also observed for aortic systolic pressure (aoSP) [119(114-130) vs 135(125-147) mmHg, P = .002] and cf-PWV (9.2 ± 1.6 vs 11.1 ± 1.5 m/s, P < .001). The urinary Na/K ratio presented significant correlations with proteinuria (r = .27, P = .023), CRP (r = .77, P < .001), cf-PWV (r = .41, P < .001), and post-occlusive reactive hyperemia on cutaneous vascular conductance (PORH CVC) (r = -.23, P = .047). By multivariate linear regression, it was detected an independent and significant association of cf-PWV with urinary Na/K ratio (R2  = 0.17, P < .001) and PORH CVC with CRP (R2  = 0.30, P = .010). Our data indicated that increased urinary Na/K ratio in non-diabetic hypertensive patients was associated with higher degree of inflammation, raised peripheral and central pressure levels, and changes suggestive of endothelial dysfunction and arterial stiffness.

Insulin reference intervals in Brazilian adolescents by direct and indirect approaches: validation of a data mining method from laboratory data

Abstract Objective To determine reference intervals (RI) for fasting blood insulin (FBI) in Brazilian adolescents, 12 to 17 years old, by direct and indirect approaches, and to validate indirectly determined RI. Methods Two databases were used for RI determination. Database 1 (DB1), used to obtain RI through a posteriori direct method, consisted of prospectively selected healthy individuals. Database 2 (DB2) was retrospectively mined from an outpatient laboratory information system (LIS) used for the indirect method (Bhattacharya method). Results From DB1, 29345 individuals were enrolled (57.65 % female) and seven age ranges and sex partitions were statistically determined according to mean FBI values: females: 12 and 13 years-old, 14 years-old, 15 years-old, 16 and 17 years-old; and males: 12, 13 and 14 years-old, 15 years-old, 16 and 17 years-old. From DB2, 5465 adolescents (67.5 % female) were selected and grouped according to DB1 partitions. The mean FBI level was significantly higher in DB2, on all groups. The RI upper limit (URL) determined by Bhattacharya method was slightly lower than the 90 % CI URL directly obtained on DB1, except for group female 12 and 13 years old. High agreement rates for diagnosing elevated FBI in all groups on DB1 validated indirect RI presented. Conclusion The present study demonstrates that Bhattacharya indirect method to determine FBI RI in adolescents can overcome some of the difficulties and challenges of the direct approach.

Effects of Nutrients and Exercises to Attenuate Oxidative Stress and Prevent Cardiovascular Disease.

BACKGROUND: In recent years, it has become more evident that oxidative stress is involved in the development of cardiovascular disease. Indeed, reactive oxygen species seems to be the common mechanism for endothelial dysfunction, vascular inflammation and arterial stiffness, resulting in a blood pressure increase and early vascular aging. METHODS: This review presents the potential role of antioxidant nutrients and exercise for cardiovascular protection. RESULTS: Flavonoids, vitamins and minerals present in some fruits and foliage are considered natural antioxidants. In fact, fruits and vegetables contain large amounts of antioxidants. Several clinical trials have extensively studied vitamin E, beta-carotene, vitamin C, polyphenols, plus selenium and zinc. In addition, many authors have been carried out clinical trials to evaluate the mechanisms of oxidative stress attenuation after exercise. Exercise responses may vary according to the Frequency, Intensity, Time and Type (FITT) principle, making it difficult to obtain a consensus concerning the exercise properties and redox status. High-intensity interval training (HIIT) has been reported as an efficient option for metabolic adaptations in a short time. Aerobic exercises must be performed at least three times a week, for two months or more, using moderate to vigorous intensity to promote a positive effect on oxidative stress and vascular function. CONCLUSION: The recognition of appropriate nutrients and exercise with antioxidant properties may be an important supportive approach to impair early vascular aging and to prevent cardiovascular disease.

Acute Effects of Whole-Body Vibration on the Pain Level, Flexibility, and Cardiovascular Responses in Individuals With Metabolic Syndrome.

The aim of the study was to assess the acute effect of whole-body vibration (WBV) exercise, with low frequency (5 Hz), on the pain level (PL), trunk flexibility, and cardiovascular responses (blood pressure [BP] and heart rate [HR]) in individuals with metabolic syndrome (MetS). Forty-four individuals were included in the study (control: 15) or in (WBV exercise: 29) groups. They were submitted to 3 bouts (1 minute each) of WBV exercise (5 Hz and peak-to-peak displacements of 2.5, 5.0, and 7.5 mm, corresponding to peak accelerations of 0.12, 0.25, and 0.35 g, respectively, sitting in a chair with the feet on the platform with knees flexed, followed by 1 minute of interset rest. The Control Group performed the same protocol, but the platform was turned off. The PL was measured through the visual analog pain scale, and the flexibility was measured through the anterior trunk flexion test. Significant improvements on PL (P = .031) and flexibility (P = .004) were found only in the WBV exercise group. The BP and HR remained at physiological levels. In conclusion, the WBV exercise would lead to physiological response decreasing PL and increasing flexibility as well as maintaining the cardiovascular responses in individuals with MetS.

Twenty-four hour Blood Pressure in Obese Patients with Moderate-to-Severe Obstructive Sleep Apnea.

BACKGROUND: Obesity, systemic arterial hypertension (SAH) and obstructive sleep apnea (OSA) are closely related. Up to 70% of patients with OSA may be asymptomatic, and there is evidence that these patients have cardiovascular disease, especially nocturnal SAH. OBJECTIVES: The aim of this study was to evaluate 24-hour blood pressure circadian variation in asymptomatic, obese individuals with moderate-to-severe OSA and compare it with that in individuals with mild OSA or without OSA. METHODS: Eighty-six obese subjects aged between 30 and 55 years (BMI 30-39 kg/m2), with casual blood pressure < 140/90 mmHg and without comorbidities were recruited. Eighty-one patients underwent clinical and anthropometric assessment, ambulatory blood pressure monitoring (ABPM), and Watch-PAT. Participants were divided into two groups, based on the apnea-hypopnea index (AHI): group 1, with AHI < 15 events/hour, and group 2 with AHI ≥ 15 events/hour. RESULTS: Compared with group 1, group 2 had higher neck circumference and waist-hip circumference (40.5 ± 3.2 cm vs. 38.0 ± 3.7 cm, p = 0.002, and 0.94 ± 0.05 vs. 0.89 ± 0.05, p = 0.001, respectively), higher systolic and diastolic blood pressure measured by the 24-h ABPM (122 ± 6 vs 118 ± 8 mmHg, p = 0.014, and 78 ± 6 vs 73 ± 7 mmHg, p = 0.008, respectively), and higher nocturnal diastolic pressure load (44,6 ± 25,9% vs 31,3 ± 27,3%, p = 0,041). Moreover, there was a positive correlation between nocturnal diastolic blood pressure and AHI (r = 0.43, p < 0.05). CONCLUSIONS: Asymptomatic obese subjects with moderate-to-severe OSA have higher systolic and diastolic blood pressure at 24 hours compared with those with absent / mild OSA, despite normal casual blood pressure between the groups. These results indicate that ABPM may be useful in the evaluation of asymptomatic obese patients with moderate-to-severe OSA.

Oral magnesium supplementation improves endothelial function and attenuates subclinical atherosclerosis in thiazide-treated hypertensive women.

BACKGROUND: Epidemiological studies demonstrate an inverse association between serum magnesium and incidence of cardiovascular disease. Diuretics commonly cause hypomagneseamia. METHOD: We evaluated effects of magnesium supplementation on blood pressure (BP) and vascular function in thiazide-treated hypertensive women in a randomized, double-blind, clinical trial. Hypertensive women (40-65 years) on hydrochlorothiazide and mean 24-h BP at least 130/80 mmHg were divided into placebo and supplementation (magnesium chelate 600 mg/day) groups. Patients were evaluated for nutritional and biochemical parameters, office and ambulatory blood pressure monitoring, brachial flow-mediated dilatation (FMD), peripheral arterial tonometry, assessment of carotid intima-media thickness, central hemodynamic parameters and pulse wave velocity at inclusion and after 6-month follow-up. RESULTS: The magnesium group had a significant reduction in SBP (144 ±â€Š17 vs. 134 ±â€Š14 mmHg, P = 0.036) and DBP (88 ±â€Š9 vs. 81 ±â€Š8 mmHg, P = 0.005) at 6 months, without effect on plasma glucose, lipids, or arterial stiffness parameters. The placebo group showed a significant increase in carotid intima-media thickness (0.78 ±â€Š0.13 vs. 0.89 ±â€Š0.14 mm, P = 0.033) without change in the magnesium group (0.79 ±â€Š0.16 vs. 0.79 ±â€Š0.19 mm, P = 0.716) after 6 months. The magnesium group demonstrated a significant increase in variation of FMD vs. the placebo group (+3.7 ±â€Š2.1 vs. 2.4 ±â€Š1.2%, P = 0.015). There was a significant correlation between the intracellular magnesium variation and FMD (r = 0.44, P = 0.011). CONCLUSION: Magnesium supplementation was associated with better BP control, improved endothelial function and amelioration of subclinical atherosclerosis in these thiazide-treated hypertensive women.

Vascular smooth muscle cell peroxisome proliferator-activated receptor γ protects against endothelin-1-induced oxidative stress and inflammation.

AIMS: Peroxisome proliferator-activated receptor γ (PPARγ) agonists reduce blood pressure and vascular injury in hypertensive rodents. Pparγ inactivation in vascular smooth muscle cells (VSMC) enhances vascular injury. Transgenic mice overexpressing endothelin (ET)-1 selectively in the endothelium (eET-1) exhibit endothelial dysfunction, increased oxidative stress and inflammation. We hypothesized that inactivation of the Pparγ gene in VSMC (smPparγ-/-) would exaggerate ET-1-induced vascular injury. METHODS AND RESULTS: eET-1, smPparγ-/- and eET-1/smPparγ-/- mice were treated with tamoxifen for 5 days and studied 4 weeks later. SBP was higher in eET-1 and unaffected by smPparγ inactivation. Mesenteric artery vasodilatory responses to acetylcholine were impaired only in smPparγ-/-. N(omega)-Nitro-L-arginine methyl ester abrogated relaxation responses, and the Ednra/Ednrb mRNA ratio was decreased in eET-1/smPparγ-/-, which could indicate that nitric oxide production was enhanced by ET-1 stimulation of endothelin type B receptors. Mesenteric artery media/lumen was greater only in eET-1/smPparγ-/-. Mesenteric artery reactive oxygen species increased in smPparγ and were further enhanced in eET-1/smPparγ-/-. Perivascular fat monocyte/macrophage infiltration was higher in eET-1 and smPparγ and increased further in eET-1/smPparγ-/-. Spleen CD11b+ cells were increased in smPparγ-/- and further enhanced in eET-1/smPparγ-/-, whereas Ly-6C(hi) monocytes increased in eET-1 and smPparγ-/- but not in eET-1/smPparγ-/-. Spleen T regulatory lymphocytes increased in smPparγ and decreased in eET-1, and decreased further in eET-1/smPparγ-/-. CONCLUSION: VSMC Pparγ inactivation exaggerates ET-1-induced vascular injury, supporting a protective role for PPARγ in hypertension through modulation of pro-oxidant and proinflammatory pathways. Paradoxically, ET-1 overexpression preserved endothelial function in smPparγ-/- mice, presumably by enhancing nitric oxide through stimulation of endothelin type B receptors.

QUALITY OF LIFE OF PATIENTS WITH METABOLIC SYNDROME IS IMPROVED AFTER WHOLE BODY VIBRATION EXERCISES.

BACKGROUND: Whole body vibration exercises (WBVE) improve the quality of life (QoL) of different populations. Metabolic syndrome patients (MetS) may be favored by physical activity. Questionnaires are used to assess the QoL. The aim was to evaluate the QoL of patients with MetS that have undergone WBVE with a brief WHOQOL (WHOQOL-BREF). MATERIAL AND METHODS: MetS patients were randomly divided into three groups: (i) control group (CG), (ii) treated with WBVE once per week (WBVE1) and (iii) treated with WBVE twice per week (WBVE2). In the first session, the patient was sat in a chair in front of the platform with the feet on its base in 3 peak to peak displacements (2.5, 5.0 and 7.5 mm) and frequency of 5 Hz was used. From the second to the last session, patients were subjected to the same protocol, however they were standing on the base of the platform and the frequency was increased up to 14 Hz. The patients fulfilled the WHOQOL-BREF before the first and after the last sessions. Cronbach coefficients were determined to each domain of the WHOQOL-BREF and test Wilcoxon (p<0.05) was used. RESULTS: The patients of the WBVE1 group had improvements in the physical, psychological and environment domains while in the WBVE2, the improvements were in the physical and social relationships domain of the WHOQOL-BREF. CONCLUSION: It was observed that the WBVE in a protocol (one or two times per week) with a progressive and increased frequency improves the QoL of patients with MetS in different domains of the WHOQOL-BREF.

Comparison of benazepril and losartan on endothelial function and vascular stiffness in patients with Type 2 diabetes mellitus and hypertension: A randomized controlled trial.

INTRODUCTION: The purpose of this study was to compare the effects of benazepril and losartan on endothelial function and vascular stiffness, in patients with diabetes mellitus and hypertension. MATERIALS AND METHODS: We included hypertensive diabetic patients with an office systolic blood pressure (BP) ⩾ 130 mmHg and/or diastolic BP ⩾ 80 mmHg. Patients were rolled over to amlodipine for 6 weeks, then we performed C-reactive protein assays, BP measurement and vascular tests; next, patients were randomized to benazepril or losartan. The tests were repeated after 12 weeks. RESULTS: We randomized 14 patients to benazepril and 16 to losartan. There were no differences in systolic (139 versus 134 mmHg, p = 0.618) and diastolic (82 versus 80 mmHg, p = 0.950) BP at the end of the study. C-reactive protein values were lower in the benazepril group (0.38 versus 0.42 mg/dl, p = 0.020). There was a slightly higher flow-mediated vasodilation (FMD) response in the benazepril group (45% increase, p = 0.057) than in the losartan group (19% increase, p = 0.132). Both central systolic BP (129 versus 123 mmHg, p = 0.934) and carotid-femoral pulse wave velocity (cfPWV) (8.5 versus 8.5 m/s, p = 0.280) were the same between groups. CONCLUSIONS: Hypertensive diabetic patients using benazepril had a greater reduction in C-reactive protein, and a slight improvement in FMD, than those taking losartan.

Small artery mechanics in hyperhomocysteinemic mice: effects of angiotensin II.

OBJECTIVE: Elevated plasma homocysteine has been associated with cardiovascular disease, although a causal relationship is unclear. The purpose of this study was to evaluate whether mild hyperhomocysteinemia (H-Hcy) may increase vascular stiffness of small arteries. METHODS: Wild-type (+/+) and heterozygous (+/-) methylenetetrahydrofolate reductase (Mthfr) knockout mice, a new model of mild H-Hcy, were treated with vehicle or angiotensin (Ang) II infusion (400 ng/kg per min s.c.). Second-order mesenteric arteries were studied on pressurized myograph. They were exposed to intraluminal pressures ranging from 3 to 140 mmHg. Media thickness and lumen diameter were measured at each pressure level to determine wall mechanical properties. Collagen type I/III and elastin deposition in the vascular wall were evaluated by confocal immunofluorescence microscopy. RESULTS: Media-to-lumen ratio was similar in Mthfr and Mthfr mice, and significantly increased by Ang II. The stress-strain relationship was shifted to the left in small mesenteric arteries from Mthfr compared to Mthfr mice, indicating that mild H-Hcy is associated with stiffer vessels. Ang II treatment in Mthfr mice enhanced the leftward shift in the stress-strain relationship and significantly increased the elastic modulus, suggesting the presence of stiffer wall components in small arteries in these animals. Increased collagen type I/III accumulation and decreased elastin content in the media of mesenteric arteries was noted in Mthfr compared to Mthfr mice. Ang II infusion augmented vascular collagen deposition in both groups, more substantially in Mthfr mice. CONCLUSIONS: Mild hyperhomocysteinemia is associated with stiffer small arteries with increased collagen deposition in the media. These changes are accentuated by Ang II-induced blood pressure elevation.

Altered vascular structure and wave reflection in hypertensive women with low magnesium levels.

Magnesium has been implicated in the pathogenesis of hypertension, but the role of its intracellular levels in cardiovascular diseases is not clear yet. We investigated the relationships of low concentrations of serum magnesium (sMg) and intracellular Mg (iMg) with clinical and vascular parameters. Thiazide-treated hypertensive women were separated into two groups according to lower (<2.0 mg/dL) or normal (≥2.0 mg/dL) sMg concentrations. The same patients were later divided according to lower (<3.75 mg/dL erythrocytes) and normal (≥3.75 mg/dL erythrocytes) iMg concentrations. Carotid ultrasound, radial applanation, and peripheral arterial tonometry were performed in all patients. Low sMg levels were associated with increased Framingham Risk Score (16% ± 3% vs 11% ± 1%; P = .024), higher systolic (148 ± 7 vs 135 ± 3 mm Hg; P = .049) and diastolic (91 ± 3 vs 84 ± 2 mm Hg; P = .042) blood pressure, and carotid intima-media thickness (0.92 ± 0.09 vs 0.76 ± 0.02 mm; P = .023). Low concentrations of iMg were related to wave reflection parameters such as increased augmentation pressure (20 ± 2 vs 15 ± 1 mm Hg; P = .032) and augmentation index (43% ± 2% vs 33% ± 2%; P = .004). In conclusion, in these diuretic-treated hypertensive women, low sMg was associated with higher blood pressure values, and more intense wave reflection were closely linked to iMg depletion, processes that might contribute to hypertension and other cardiovascular risk factors.

Protective role of vascular smooth muscle cell PPARγ in angiotensin II-induced vascular disease.

AIMS: Vascular peroxisome proliferator-activated receptor γ (PPARγ) activation improves vascular remodelling and endothelial function in hypertensive rodents. The goal of this study was to determine that vascular smooth muscle cell (VSMC) PPARγ exerts a vascular protective role beyond its metabolic effects. METHODS AND RESULTS: We generated a model of adult inducible VSMC-specific Pparγ inactivation to test the hypothesis that PPARγ counteracts angiotensin (Ang) II-induced vascular remodelling and endothelial dysfunction. Inducible VSMC Pparγ knockout mice were generated by crossing Pparγ floxed mice with mice expressing a tamoxifen-inducible Cre recombinase Smooth muscle (Sm) myosin heavy chain promoter control. Eight-to-ten-week-old SmPparγ(-/-) and control mice were infused with a nonpressor dose of Ang II for 7 days. Blood pressure was unaffected. Mesenteric arteries showed eutrophic remodelling in Ang II-infused control mice and hypertrophic remodelling in Ang II-infused SmPparγ(-/-) mice. Endothelium-dependent relaxation to acetylcholine was reduced in SmPparγ(-/-) mice and further impaired by Ang II infusion, and was unaffected by an inhibitor of NO synthase, suggesting a defect of NO-mediated relaxation. SmPparγ deletion increased the sensitivity to Ang II-induced contraction. SmPparγ(-/-) mice exhibited enhanced Ang II-induced vascular NADPH oxidase activity and adhesion molecule ICAM-1 and chemokine monocyte chemotactic protein-1 expression. The antioxidant Superoxide dismutase 3 expression was decreased by SmPparγ deletion. Ang II infusion increased the expression of CD3 T-cell co-receptor chain δ and decreased Adiponectin in perivascular adipose tissue of SmPparγ(-/-) mice. CONCLUSION: Inducible Pparγ inactivation in VSMCs exacerbated Ang II-induced vascular remodelling and endothelial dysfunction via enhanced vascular oxidative stress and inflammation, revealing the protective role of VSMC PPARγ in angiotensin II-induced vascular injury.