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.

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.

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.

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.

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.

Matrix metalloproteinases and left ventricular function and structure in spinal cord injured subjects.

Subjects with spinal cord injury (SCI) exhibit impaired left ventricular (LV) diastolic function, which has been reported to be attenuated by regular physical activity. This study investigated the relationship between circulating matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) and echocardiographic parameters in SCI subjects and the role of physical activity in this regard. Forty-two men with SCI [19 sedentary (S-SCI) and 23 physically-active (PA-SCI)] were evaluated by clinical, anthropometric, laboratory, and echocardiographic analysis. Plasmatic pro-MMP-2, MMP-2, MMP-8, pro-MMP-9, MMP-9, TIMP-1 and TIMP-2 levels were determined by enzyme-linked immunosorbent assay and zymography. PA-SCI subjects presented lower pro-MMP-2 and pro-MMP-2/TIMP-2 levels and improved markers of LV diastolic function (lower E/Em and higher Em and E/A values) than S-SCI ones. Bivariate analysis showed that pro-MMP-2 correlated inversely with Em and directly with E/Em, while MMP-9 correlated directly with LV mass index and LV end-diastolic diameter in the whole sample. Following multiple regression analysis, pro-MMP-2, but not physical activity, remained associated with Em, while MMP-9 was associated with LV mass index in the whole sample. These findings suggest differing roles for MMPs in LV structure and function regulation and an interaction among pro-MMP-2, diastolic function and physical activity in SCI subjects.

Physical activity and improved diastolic function in spinal cord-injured subjects.

PURPOSE: Subjects with spinal cord injury (SCI) have been reported to present impaired left ventricular (LV) diastolic function in comparison with able-bodied (AB) ones. The present study investigated the effect of regular physical activity on the cardiac structure and function of SCI subjects. METHODS: Fifty-eight SCI men (29 sedentary [SCI-S] and 29 athletes [SCI-A]) and 29 AB men were cross-sectionally evaluated by clinical, laboratory, hemodynamic, and echocardiographic analysis. All enrolled subjects were normotensive, nondiabetic, nonsmoker, and normolipemic, and the studied groups presented similar age and body mass index. RESULTS: SCI-S presented similar LV structural and systolic parameters but higher E/Em (8.0 ± 0.5) and lower Em/Am (1.18 ± 0.09) ratios than SCI-A and AB (E/Em = 6.4 ± 0.3 and 5.9 ± 0.3, respectively; Em/Am = 1.57 ± 0.12 and 1.63 ± 0.08, respectively; all P < 0.05 compared with SCI-S). Analysis of SCI individuals according to injury level revealed that tetraplegic athletes had similar features compared with sedentary tetraplegic subjects, except for higher Em (10.9 ± 0.6 vs 8.6 ± 0.7 cm s, P < 0.05) and lower E/Em ratio (6.3 ± 0.4 vs 8.8 ± 0.8, P < 0.05), whereas paraplegic athletes had similar features compared with sedentary paraplegic individuals, except for higher LV end-diastolic diameter (49.4 ± 1.4 vs 45.0 ± 1.0 mm, P < 0.05) and Em/Am ratio (1.69 ± 0.20 vs 1.19 ± 0.08, P < 0.05) and lower LV relative wall thickness (0.330 ± 0.012 vs 0.369 ± 0.010, P < 0.05) and heart rate (67.1 ± 4.2 vs 81.9 ± 2.8 bpm, P < 0.05). CONCLUSION: Regular physical activity is associated with improved LV diastolic function in SCI subjects and might exert distinct cardiac structural effects in tetraplegic and paraplegic subjects.

Oxidized low-density lipoprotein, matrix-metalloproteinase-8 and carotid atherosclerosis in spinal cord injured subjects.

OBJECTIVE: Previous reports have indicated that subjects with chronic spinal cord injury (SCI) exhibit increased cardiovascular risk compared to able-bodied individuals. This study investigated the relationship between plasmatic oxidized low-density lipoprotein (OxLDL), matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) levels and vascular remodeling in SCI subjects and the role of physical activity in this regard. METHODS: We studied 42 men with chronic (≥2 years) SCI [18 sedentary (S-SCI) and 24 physically active (PA-SCI)] and 16 able-bodied men by clinical, anthropometric, laboratory, and carotid intima-media thickness (IMT) analysis. All enrolled subjects were normotensive, non-diabetics, non-smokers and normolipemic. Plasmatic OxLDL, MMP-2, MMP-8, MMP-9, TIMP-1 and TIMP-2 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Carotid IMT, IMT/diameter ratio and OxLDL levels of PA-SCI and able-bodied subjects were statistically similar. Conversely, S-SCI subjects exhibited higher IMT, IMT/diameter ratio and OxLDL levels compared to PA-SCI (p < 0.01, p < 0.001 and p = 0.01, respectively) and able-bodied (p < 0.001 for all) individuals. Results of bivariate correlation analysis including all injured subjects showed that carotid IMT and IMT/diameter ratio only correlated with OxLDL, MMP-8 and MMP-8/TIMP-1 ratio. Further stepwise regression analysis adjusted for the presence or not of physical activity and age showed that OxLDL was associated with carotid IMT and IMT/diameter ratio, while MMP-8 was associated with IMT/diameter ratio in SCI individuals. CONCLUSIONS: Plasmatic OxLDL and MMP-8 levels are associated with carotid atherosclerosis and there is an interaction among physical inactivity, atherosclerosis and OxLDL in SCI individuals.