Impact of Regular Physical Activity on Adipocytokines and Cardiovascular Characteristics in Spinal Cord-Injured Subjects.

OBJECTIVE: To investigate the relationship of carotid artery intima-media thickness (IMT) and cardiac structure and function with adipocytokines in sedentary (S-SCI) and physically active (PA-SCI) subjects with spinal cord injury (SCI). DESIGN: Cross-sectional observational study. SETTING: Academic medical center. PARTICIPANTS: Men with chronic (>1y) SCI (N=41; 16 S-SCI, 25 PA-SCI) were evaluated. S-SCI subjects did not perform labor that required physical effort, recreational physical activity, or sports, while PA-SCI subjects included competing athletes who were regularly performing adapted sports. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Clinical, laboratory, carotid ultrasonography, and echocardiography analysis. Plasma leptin, adiponectin, and plasminogen activating inhibitor-1 (PAI-1) levels were determined. RESULTS: PA-SCI subjects had similar levels of adipocytokines, but lower carotid IMT and carotid IMT/diameter, and better left ventricular diastolic function than S-SCI participants. Bivariate analysis showed that adiponectin was inversely correlated with triglycerides (r=-.85, P<.001), low-density lipoprotein cholesterol (r=-.57, P<.05), and carotid IMT/diameter (r=-.56, P<.05) in S-SCI but not in PA-SCI participants. Additionally, the leptin-adiponectin ratio showed a direct correlation with triglycerides (r=.84, P<.001) and low-density lipoprotein cholesterol (r=.53, P<.05) in S-SCI but not in PA-SCI individuals. By contrast, the studied adipocytokines did not correlate with cardiac structure and function in PA-SCI and S-SCI participants. CONCLUSIONS: Lower adiponectin levels and higher leptin-adiponectin ratio are related to adverse vascular and/or metabolic characteristics in individuals with SCI. This relationship, however, appears to be mitigated by regular physical activity.

Impact of Adapted Sports Activities on the Progression of Carotid Atherosclerosis in Subjects With Spinal Cord Injury.

OBJECTIVE: To determine whether regular performance of adapted sports is associated with long-term changes in carotid atherosclerosis in subjects with spinal cord injury (SCI). DESIGN: Prospective observational study. SETTING: Academic medical center. PARTICIPANTS: Men with chronic (>1y) SCI and no preserved motor function below the injury level were evaluated in 2007 and 2012 (N=17). Nine subjects did not perform physical activity between the studied time points (control group), whereas 8 subjects entered competitive upper-body sports programs (rugby: n=5, basketball: n=1, jiu-jitsu: n=1, and tennis: n=1) after baseline and were regularly training at the time of the second evaluation (sports group). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Clinical, laboratory, hemodynamic, and carotid ultrasonography analysis. RESULTS: The studied groups showed no differences in all studied variables at baseline. After 5 years of follow-up, the control group showed increases in heart rate (87.0±3.1 vs 74.7±3.8 beats per minute; P=.004), but the participants had no significant changes in carotid intima-media thickness (IMT) (.65±.05 vs .67±.03mm; P=.73) or IMT/diameter (.118±.007 vs .136±.013; P=.24). In contrast, the sports group showed long-term decreases in carotid IMT (.56±.05 vs .74±.05mm; P=.001) and IMT/diameter (.097±.006 vs .141±.009; P<.001), but the participants did not show any variation in the other studied variables at follow-up. CONCLUSIONS: Regular upper-body sports activities are associated with long-term reductions in carotid atherosclerosis in subjects with SCI and might be a potential prevention strategy aiming to reduce cardiovascular risk in this population.

Relationship of blood pressure measured in the calf with arm blood pressure and arterial stiffness: a general population study.

AIM: Leg blood pressure (BP) measurement is needed when arm BP evaluation is not feasible, and calf BP, especially when measured in standing position, may have greater association with cardiovascular remodeling than arm BP. This study evaluated the relationship between calf and arm BP, and investigated whether calf BP would be superior to arm BP in predicting increased arterial stiffness [pulse wave velocity (PWV) > 10 m/s]. METHODS: We evaluated clinical and laboratory characteristics, BP measurements, and PWV in 1397 individuals resident in Baependi, Brazil, between 2017 and 2019. Arm BP was measured in the seated and supine positions while calf BP was measured in supine and standing positions using digital oscillometric devices. Carotid-femoral PWV was measured using a noninvasive mechanotransducer. RESULTS: The sample had 62.7% females, age = 48.1 ±â€Š15.4 years and 8.4% with PWV >10 m/s. Results of linear regression analysis showed that BP values of 140/90 mmHg measured in the arm in supine and seated position were equivalent to calf supine BP values of 164/81 mmHg and 166/78 mmHg and calf standing BP values of 217/137 mmHg and 221/137 mmHg, respectively. Calf-arm BP differences were associated with age, glomerular filtration rate, body mass index, smoking, low-density lipoprotein-cholesterol, diabetes and height. Furthermore, stepwise logistic regression analysis revealed that arm supine systolic BP, but not calf BP measurements, was independently associated with increased arterial stiffness. CONCLUSION: Thresholds of ≈165/80 mmHg and ≈220/135 mmHg could be used for diagnosing hypertension when only calf measurements in supine and standing positions, respectively, are available. Conversely, calf BP was not superior to arm BP in predicting increased arterial stiffness.

Impaired Cardiac Sympathetic Activity Is Associated With Myocardial Remodeling and Established Biomarkers of Heart Failure.

BACKGROUND: 123Iodine-meta-iodobenzylguanidine scintigraphy is useful for assessing cardiac autonomic dysfunction and predict outcomes in heart failure (HF). The relationship of cardiac sympathetic function with myocardial remodeling and diffuse fibrosis remains largely unknown. We aimed to evaluate the cardiac sympathetic function of patients with HF and its relation with myocardial remodeling and exercise capacity. METHODS AND RESULTS: Prospectively enrolled patients with HF (New York Heart Association class II-III) were stratified into HF with preserved left ventricular ejection fraction [LVEF] ≥45%) and reduced LVEF. Ventricular morphology/function and myocardial extracellular volume (ECV) fraction were quantified by cardiovascular magnetic resonance, global longitudinal strain by echocardiography, cardiac sympathetic function by heart-to-mediastinum ratio from 123iodine-meta-iodobenzylguanidine scintigraphy. All participants underwent cardiopulmonary exercise testing. The cohort included 33 patients with HF with preserved LVEF (LVEF, 60±10%; NT-proBNP [N-terminal pro-B-type natriuretic peptide], 248 [interquartile range, 79-574] pg/dL), 28 with HF with reduced LVEF (LVEF, 30±9%; NT-proBNP, 743 [interquartile range, 250-2054] pg/dL) and 20 controls (LVEF, 65±5%; NT-proBNP, 40 [interquartile range, 19-50] pg/dL). Delayed (4 hours) 123iodine-meta-iodobenzylguanidine heart-to-mediastinum ratio was lower in HF with preserved LVEF (1.59±0.25) and HF with reduced LVEF (1.45±0.16) versus controls (1.92±0.24; P<0.001), and correlated negatively with diffuse fibrosis assessed by ECV (R=-0.34, P<0.01). ECV in segments without LGE was increased in HF with preserved ejection fraction (0.32±0.05%) and HF with reduced left ventricular ejection fraction (0.31±0.04%) versus controls (0.28±0.04, P<0.05) and was associated with the age- and sex-adjusted maximum oxygen consumption (peak oxygen consumption); (R=-0.41, P<0.01). Preliminary analysis indicates that cardiac sympathetic function might potentially act as a mediator in the association between ECV and NT-proBNP levels. CONCLUSIONS: Abnormally low cardiac sympathetic function in patients with HF with reduced and preserved LVEF is associated with extracellular volume expansion and decreased cardiopulmonary functional capacity.

Profile of serum microRNAs in heart failure with reduced and preserved ejection fraction: Correlation with myocardial remodeling.

Background and aims: Cardiomyocyte hypertrophy and interstitial fibrosis are key components of myocardial remodeling in Heart Failure (HF) with preserved (HFpEF) or reduced ejection fraction (HFrEF). MicroRNAs (miRNAs) are non-coding, evolutionarily conserved RNA molecules that may offer novel insights into myocardial remodeling. This study aimed to characterize miRNA expression in HFpEF (LVEF ≥ 45%) and HFrEF (LVEF < 45%) and its association with myocardial remodeling. Methods: Prospectively enrolled symptomatic HF patients (HFpEF:n = 36; HFrEF:n = 31) and controls (n = 23) underwent cardiac magnetic resonance imaging with T1-mapping and circulating miRNA expression (OpenArray system). Results: 13 of 188 miRNAs were differentially expressed between HF groups (11 downregulated in HFpEF). Myocardial extracellular volume (ECV) was increased in both HF groups (HFpEF 30 ± 5%; HFrEF 30 ± 3%; controls 26 ± 2%, p < 0.001). miR-128a-3p, linked to cardiac hypertrophy, fibrosis, and dysfunction, correlated positively with ECV in HFpEF (r = 0.60, p = 0.01) and negatively in HFrEF (r = -0.51, p = 0.04). miR-423-5p overexpression, previously associated HF mortality, was inversely associated with LVEF (r = - 0.29, p = 0.04) and intracellular water lifetime (τic) (r = -0.45, p < 0.05) in both HF groups, and with NT-proBNP in HFpEF (r = -0.63, p < 0.01). Conclusions: miRNA expression profiles differed between HF phenotypes. The differential expression and association of miR-128a-3p with ECV may reflect the distinct vascular, interstitial, and cellular etiologies of HF phenotypes.

Pathophysiological effects of SARS-CoV-2 infection on the cardiovascular system and its clinical manifestations-a mini review.

Coronavirus disease 2019 (COVID-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 may have a mild presentation, with few symptoms, or progress to a severe condition, characterized by generalized inflammation, systemic microvascular involvement, coagulopathy, and pulmonary and cardiovascular complications. Men present with more severe symptoms than women, especially men who are older and who present with comorbidities such as hypertension, diabetes mellitus, and a history of atherosclerotic diseases. Owing to its association with endothelial dysfunction, inflammation, thrombosis, and microvascular obstruction, SARS-CoV-2 infection can cause lesions in several organs, including the myocardium and the coronary arterial bed, which can result in clinical manifestations involving the cardiovascular system. In this mini review, we summarize the effects of SARS-CoV-2 infection on the cardiovascular system in both children and adults and characterize the various clinical manifestations associated with this disease.

Determinants and prognostic value of in-hospital infection in patients waiting for permanent pacemaker implantation.

BACKGROUND: In-hospital delays in permanent cardiac pacemaker (PPM) implantation are common and may result in in-hospital infection among patients waiting for PPM implantation (pre-PPM-HI). This study investigated the predictors and prognostic impact of these events. METHODS: We retrospectively evaluated 905 consecutive patients (68.2 ± 16.0 years; 54% males) who underwent PPM implantation. Clinical characteristics, pre-PPM-HI and 30-day mortality were recorded and a risk score for pre-PPM-HI was generated using multivariable logistic regression coefficients. RESULTS: Eigthy-nine patients (10% of the sample) developed pre-PPM-HI. Multivariable logistic regression analysis identified urinary catheter use, complete atrioventricular block, implantation of temporary pacemaker and diabetes mellitus as independent predictors of pre-PPM-HI. The generated score (range 0-10.1) played a better role in predicting pre-PPM-HI than individual factors, yielding an area under the curve [95%CI] of 0.754 [0.705-0.803]. Patients with score ≥ 7.5 had 18-fold greater risk of developing pre-PPM-HI than those with score < 2.5. Furthermore, multivariable Cox-regression analysis showed that patients who developed pre-PPM-HI had greater 30-day mortality after PPM implantation (hazard ratio [95%CI] = 2.90 [1.18-7.16], p = 0.021) compared with their counterparts. CONCLUSIONS: This study reveals that pre-PPM-HI is an independent predictor of early mortality after PPM implantation. In addition, a clinical score developed from simple clinical variables accurately identified patients at high risk of pre-PPM-HI. In scenarios where delays in PPM implantation are unavoidable, such as reference hospitals with high demand, the use of this tool can potentially help in the hierarchy of patients and in the reduction of this adverse event.

Relationship Between Circulating MicroRNAs and Left Ventricular Hypertrophy in Hypertensive Patients.

Objective: Left ventricular hypertrophy (LVH) is a common complication of hypertension and microRNAs (miRNAs) are considered to play an important role in cardiac hypertrophy development. This study evaluated the relationship between circulating miRNAs and LVH in hypertensive patients. Methods: Two cohorts [exploratory (n = 42) and validation (n = 297)] of hypertensive patients were evaluated by clinical, laboratory and echocardiography analysis. The serum expression of 754 miRNAs in the exploratory cohort and 6 miRNAs in the validation cohort was evaluated by the TaqMan OpenArray® system and quantitative polymerase chain reaction, respectively. Results: Among the 754 analyzed miRNAs, ten miRNAs (miR-30a-5p, miR-let7c, miR-92a, miR-451, miR-145-5p, miR-185, miR-338, miR-296, miR-375, and miR-10) had differential expression between individuals with and without LVH in the exploratory cohort. Results of multivariable regression analysis adjusted for confounding variables showed that three miRNAs (miR-145-5p, miR-451, and miR-let7c) were independently associated with LVH and left ventricular mass index in the validation cohort. Functional enrichment analysis demonstrated that these three miRNAs can regulate various genes and pathways related to cardiac remodeling. Furthermore, in vitro experiments using cardiac myocytes demonstrated that miR-145-5p mimic transfection up-regulated the expression of brain and atrial natriuretic peptide genes, which are markers of cardiac hypertrophy, while anti-miR-145-5p transfection abrogated the expression of these genes in response to norepinephrine stimulus. Conclusions: Our data demonstrated that circulating levels of several miRNAs, in particular miR-145-5p, miR-451, and let7c, were associated with LVH in hypertensive patients, indicating that these miRNAS may be potential circulating biomarkers or involved in hypertension-induced LV remodeling.

Association of carotid wall layers with atherosclerotic plaques and cardiac hypertrophy in hypertensive subjects.

Carotid intima-media thickness (cIMT) is considered a marker of subclinical atherosclerosis and is related to target-organ damage in hypertensive patients. However, increased cIMT may be due to increases in the thickness of intima (cIT) and media (cMT) layers. This study evaluated whether cIMT layers (cIT and cMT) had a greater association with carotid atherosclerotic plaques and left ventricular hypertrophy (LVH) than cIMT in hypertensive subjects. We cross-sectionally evaluated clinical, carotid, and echocardiography characteristics of 186 hypertensive patients followed at an outpatient clinic. High-resolution images of common carotid arteries were obtained by ultrasonography equipped with 10-MHz transducers, and cIT, cMT, and cIMT were manually measured using an image-processing software. Among all participants (n = 186; age = 60.8 ± 10.9 years, 43% males), there were 58% with carotid plaques and 58% with LVH. Mean cIT, cMT, and cIMT values were 0.267 ± 0.060, 0.475 ± 0.107, and 0.742 ± 0.142 mm, respectively. In logistic regression analysis adjusted for relevant covariates, carotid plaques showed stronger association with cIT than with cMT and cIMT. Furthermore, cIT showed greater area under the ROC curve (0.92; 95% CI 0.87-0.96) than cIMT (0.79; 95% CI 0.72-0.85) and cMT (0.64; 95% CI 0.56-0.72) to identify plaques. Conversely, cIT, cMT, and cIMT had modest association and accuracy to identify LVH (area under the ROC curve = 0.61, 0.57, and 0.60, respectively). In conclusion, cIT is a more accurate marker of atherosclerosis than cMT or cIMT, while cIT and cMT provide no incremental value in identifying LVH when compared with cIMT among hypertensive subjects.

Increased Serum Mir-150-3p Expression Is Associated with Radiological Lung Injury Improvement in Patients with COVID-19.

Coronavirus disease 2019 (COVID-19) is caused by the SARS-CoV-2 virus, responsible for an atypical pneumonia that can progress to acute lung injury. MicroRNAs are small non-coding RNAs that control specific genes and pathways. This study evaluated the association between circulating miRNAs and lung injury associated with COVID-19. Methods: We evaluated lung injury by computed tomography at hospital admission and discharge and the serum expression of 754 miRNAs using the TaqMan OpenArray after hospital discharge in 27 patients with COVID-19. In addition, miR-150-3p was validated by qRT-PCR on serum samples collected at admission and after hospital discharge. Results: OpenArray analysis revealed that seven miRNAs were differentially expressed between groups of patients without radiological lung improvement compared to those with lung improvement at hospital discharge, with three miRNAs being upregulated (miR-548c-3p, miR-212-3p, and miR-548a-3p) and four downregulated (miR-191-5p, miR-151a-3p, miR-92a-3p, and miR-150-3p). Bioinformatics analysis revealed that five of these miRNAs had binding sites in the SARS-CoV-2 genome. Validation of miR-150-3p by qRT-PCR confirmed the OpenArray results. Conclusions: The present study shows the potential association between the serum expression of seven miRNAs and lung injury in patients with COVID-19. Furthermore, increased expression of miR-150 was associated with pulmonary improvement at hospital discharge.

The C242T polymorphism of the p22-phox gene (CYBA) is associated with higher left ventricular mass in Brazilian hypertensive patients.

BACKGROUND: Reactive oxygen species have been implicated in the physiopathogenesis of hypertensive end-organ damage. This study investigated the impact of the C242T polymorphism of the p22-phox gene (CYBA) on left ventricular structure in Brazilian hypertensive subjects. METHODS: We cross-sectionally evaluated 561 patients from 2 independent centers [Campinas (n = 441) and Vitória (n = 120)] by clinical history, physical examination, anthropometry, analysis of metabolic and echocardiography parameters as well as p22-phox C242T polymorphism genotyping. In addition, NADPH-oxidase activity was quantified in peripheral mononuclear cells from a subgroup of Campinas sample. RESULTS: Genotype frequencies in both samples were consistent with the Hardy- Weinberg equilibrium. Subjects with the T allele presented higher left ventricular mass/height2.7 than those carrying the CC genotype in Campinas (76.8 ± 1.6 vs 70.9 ± 1.4 g/m2.7; p = 0.009), and in Vitória (45.6 ± 1.9 vs 39.9 ± 1.4 g/m2.7; p = 0.023) samples. These results were confirmed by stepwise regression analyses adjusted for age, gender, blood pressure, metabolic variables and use of anti-hypertensive medications. In addition, increased NADPH-oxidase activity was detected in peripheral mononuclear cells from T allele carriers compared with CC genotype carriers (p = 0.03). CONCLUSIONS: The T allele of the p22-phox C242T polymorphism is associated with higher left ventricular mass/height 2.7 and increased NADPH-oxidase activity in Brazilian hypertensive patients. These data suggest that genetic variation within NADPH-oxidase components may modulate left ventricular remodeling in subjects with systemic hypertension.

Sodium intake is associated with carotid artery structure alterations and plasma matrix metalloproteinase-9 upregulation in hypertensive adults.

The mechanisms by which dietary sodium modulates cardiovascular risk are not fully understood. This study investigated whether sodium intake is related to carotid structure and hemodynamics and to plasma matrix metalloproteinase (MMP) activity in hypertensive adults. One hundred thirty-four participants were cross-sectionally evaluated by clinical history, anthropometry, carotid ultrasound, and analysis of hemodynamic, inflammatory, and metabolic variables. Daily sodium intake (DSI) was estimated by 24-h recall, discretionary sodium, and a FFQ. In 42 patients, plasma MMP-2 and MMP-9 activities were also analyzed. The mean DSI was 5.52 ± 0.29 g/d. Univariate analysis showed that DSI correlated with common carotid artery systolic and diastolic diameter (r = 0.36 and 0.34; both P < 0.001), peak and mean circumferential tension (r = 0.44 and 0.39; both P < 0.001), Young's Elastic Modulus (r = 0.40; P < 0.001), intima-media thickness (r = 0.19; P < 0.05), and internal carotid artery resistive index (r = 0.20; P < 0.05). Multivariate analyses revealed that only artery diameter, circumferential wall tension, and Young's Elastic Modulus were independently associated with DSI. Conversely, plasma MMP-9 activity was associated with DSI (r = 0.53; P < 0.001) as well as with common carotid systolic diameter (r = 0.33; P < 0.05) and Young's Elastic Modulus (r = 0.38; P < 0.01). In conclusion, sodium intake is associated with carotid alterations in hypertensive adults independently of systemic hemodynamic variables. The present findings also suggest that increased MMP-9 activity might play a role in sodium-induced vascular remodeling.

Association of Circulating miR-145-5p and miR-let7c and Atherosclerotic Plaques in Hypertensive Patients.

AIM: Hypertension is a strong risk factor for atherosclerosis. Increased carotid intima-media thickness (cIMT) and carotid plaques are considered subclinical markers of atherosclerosis. This study aimed at evaluating the serum expression of miRNAs previously related to adverse vascular remodeling and correlating them with carotid plaques and cIMT in hypertensive patients. METHODS: We cross-sectionally evaluated the clinical and carotid characteristics as well as serum expression of miR-145-5p, miR-let7c, miR-92a, miR-30a and miR-451 in 177 hypertensive patients. Carotid plaques and cIMT were evaluated by ultrasound, and the expression of selected miRNAs was evaluated by a quantitative polymerase chain reaction. RESULTS: Among all participants (age = 60.6 ± 10.7 years, 43% males), there were 59% with carotid plaques. We observed an increased expression of miR-145-5p (Fold Change = 2.0, p = 0.035) and miR-let7c (Fold Change = 3.8, p = 0.045) in participants with atherosclerotic plaque when compared to those without plaque. In the logistic regression analysis adjusted for relevant covariates, these miRNAs showed a stronger association with carotid plaques (miR-145-5p: Beta ± SE = 0.050 ± 0.020, p = 0.016 and miR-let7c: Beta ± SE = 0.056 ± 0.019, p = 0.003). CONCLUSIONS: Hypertensive patients with carotid plaques have an increased expression of miR-145-5p and miR-let7c, suggesting a potential role of these miRNAs as a biomarker for subclinical atherosclerosis in hypertensive individuals.

Bioinformatics analysis of circulating miRNAs related to cancer following spinal cord injury.

Patients with spinal cord injury (SCI) have an increased risk of developing esophageal, bladder and hematologic malignancies compared with the normal population. In the present study, we aimed to identify, through in silico analysis, miRNAs and their target genes related to the three most frequent types of cancer in individuals with SCI. In a previous study, we reported a pattern of expression of miRNAs in 17 sedentary SCI males compared with 22 healthy able-bodied males by TaqMan OpenArray. This list of miRNAs deregulated in SCI patients was uploaded to miRWALK2.0 to predict the target genes and pathways of selected miRNAs. We used Cytoscape software to construct the network displaying the miRNAs and their gene targets. Among the down-regulated miRNAs in SCI, 21, 19 and 20 miRNAs were potentially associated with hematological, bladder and esophageal cancer, respectively, and three target genes (TP53, CCND1 and KRAS) were common to all three types of cancer. The three up-regulated miRNAs were potentially targeted by 18, 15 and 10 genes associated with all three types of cancer. Our current bioinformatics analysis suggests the potential influence of several miRNAs on the development of cancer in SCI. In general, these data may provide novel information regarding potential molecular mechanisms involved in the development of cancer among individuals with SCI. Further studies aiming at understanding how miRNAs contribute to the development of the major cancers that affect patients after SCI may help elucidate the role of these molecules in the pathophysiology of the disease.

Circulating microRNAs, Vascular Risk, and Physical Activity in Spinal Cord-Injured Subjects.

The aim of this study was to compare the expression of serum microRNAs (miRNAs) in individuals with spinal cord injury (SCI) (athletes [SCI-A] and sedentary [SCI-S]) and able-bodied (AB) individuals, and investigate the relationship of miRNAs with carotid intima-media thickness (cIMT) and serum oxidized LDL-cholesterol (oxLDL) among SCI subjects. Seventeen SCI-S, 23 SCI-A, and 22 AB males were evaluated by clinical and laboratory analysis, and had oxLDL and cIMT measured by enzyme-linked immunosorbent assay (ELISA) and ultrasonography, respectively. A total of 754 miRNAs were measured using a TaqMan OpenArray® Human MicroRNA system. SCI-S subjects had higher cIMT and oxLDL than SCI-A and AB. Compared with AB, only one miRNA was differently expressed in both SCI-A and SCI-S individuals, whereas 25 miRNAs were differently expressed in SCI-S, but not in SCI-A. Of these 25 miRNAs, 22 showed different expression between SCI-S and SCI-A. Several miRNAs correlated with oxLDL and cIMT among all SCI individuals. Notably, miR-125b-5p, miR-146a-5p, miR-328-3p, miR-191-5p, miR-103a-3p, and miR-30b-5p correlated with both oxLDL and cIMT, and showed distinct expression between the SCI-A and SCI-S groups. Gene set enrichment analysis demonstrated that miRNAs related to cIMT and oxLDL may be involved in molecular pathways regulating vascular function and remodeling. In conclusion, this exploratory analysis suggests that variations in circulating miRNA expression in individuals with SCI compared with AB subjects are markedly attenuated by regular physical activity. Several miRNAs may be involved in physical activity-related improvements in vascular risk and remodeling among SCI individuals.

Noninvasive imaging assessment of rehabilitation therapy in heart failure with preserved and reduced left ventricular ejection fraction (IMAGING-REHAB-HF): design and rationale.

BACKGROUND: Studies have shown significant benefits of exercise therapy in heart failure (HF) with a reduced ejection fraction (HFrEF) and HF with a preserved ejection fraction (HFpEF). The mechanisms responsible for the beneficial effect of exercise in HFrEF and HFpEF are still unclear. We hypothesized that the effect of exercise on myocardial remodeling may explain its beneficial effect. METHODS: IMAGING-REHAB-HF is a single-center, randomized, controlled clinical trial using cardiac magnetic resonance imaging, vasomotor endothelial function, cardiac sympathetic activity imaging and serum biomarkers to compare the effect of exercise therapy in HFpEF (LVEF ≥ 45%) and HFrEF (LVEF < 45%). Subjects will be assessed at baseline and after 4 months. The exercise program will consist of three 60-min exercise sessions/week. The primary endpoints are the effect of exercise on myocardial extracellular volume (ECV), left ventricular (LV) systolic function, LV mass, LV mass-to-volume and LV cardiomyocyte volume. Secondary endpoints include the effect of exercise on vasomotor endothelial function, cardiac sympathetic activity and plasmatic biomarkers. Patients will be allocated in a 2:1 fashion to supervised exercise program or usual care. A total sample size of 90 patients, divided into two groups according to LVEF:HFpEF group (45 patients:30 in the intervention arm and 15 in the control arm) and HFrEF group (45 patients:30 in the intervention arm and 15 in the control arm) - will be necessary to achieve adequate power. CONCLUSION: This will be the first study to evaluate the benefits of a rehabilitation program on cardiac remodeling in HF patients. The unique design of our study may provide unique data to further elucidate the mechanisms involved in reverse cardiac remodeling after exercise in HFpEF and HFrEF patients.

Reduced Sympathetic Stimulus and Angiotensin 1-7 Are Related to Diastolic Dysfunction in Spinal Cord-Injured Subjects.

Chronic spinal cord injury (SCI) is often associated with reductions in left ventricular (LV) diastolic function. Impairments in sympathetic activity and activation of the renin-angiotensin system are reported in SCI individuals and may hypothetically be implicated in this association. Hence, the present study verified the relationship between these two neuro-hormonal and cardiac functional and structural characteristics in SCI individuals. Twenty-two men with SCI (injury level above T6 and no voluntary motion below the injury) and 11 able-bodied men were evaluated by clinical, hemodynamic, laboratory, and echocardiographic analysis and had plasmatic renin, angiotensin I (ANGI), angiotensin II (ANGII), angiotensin 1-7 (ANG1-7), and noradrenaline levels measured. SCI subjects had lower noradrenaline (p = 0.003) and higher ANG1-7 (p = 0.009), but similar renin, ANGI, and ANGII levels when compared with able-bodied individuals. In SCI individuals, results of multi-variable analysis showed that higher Em, a marker of better LV diastolic function, was directly associated with ANG1-7 (p = 0.05) or ANG1-7/ANGII ratio (p = 0.007), whereas lower noradrenaline levels were independently associated with worse LV diastolic function, as assessed by E/Em ratio (p = 0.028). In conclusion, these results suggest that reduced sympathetic activity and expression of ANG1-7 may be involved in SCI-related diastolic dysfunction.

Gender influences the relationship between lung function and cardiac remodeling in hypertensive subjects.

Hypertensive patients are predisposed to left ventricular (LV) remodeling and frequently exhibit decline in lung function as compared with the general population. Here, we investigated the association between spirometric and echocardiographic data in non-smoking hypertensive subjects and the role of gender in this regard. In a cross-sectional study, 107 hypertensive patients (60 women) enrolled from a university outpatient clinic were evaluated by clinical, hemodynamic, laboratory and echocardiographic analysis. Vital capacity, forced vital capacity (FVC), forced expired volume in 1 s (FEV1) and in 6 s (FEV6), FEV1/FVC ratio and FEV1/FEV6 ratio were estimated by spirometry. In women, higher LV mass index and E/Em ratio correlated with markers of restrictive lung alterations, such as reduced FVC (r=-044; P<0.001; r=-0.42; P<0.001, respectively) and FEV6 (r=-0.43; P<0.001; r=-0.39; P<0.01, respectively), while higher left atrial volume index correlated with markers of obstructive lung alterations, such as reduced FEV1/FVC (r=-055; P<0.001) and FEV1/FEV6 (r=-0.45; P<0.001) ratios. These relationships were further confirmed by stepwise regression analysis adjusted for potential confounders. In men, LV mass index correlated with FVC and FEV6, but these associations did not remain statistically significant after adjustment for confounding variables. Furthermore, inflammatory markers such as plasma C-reactive protein and matrix-metalloproteinases-2 and -9 levels did not influence the association between spirometric and cardiac parameters. In conclusion, these results indicate that LV remodeling is related to restrictive lung alterations while left atrial remodeling is associated with obstructive lung alterations in hypertensive women.