Arterial Structure in 18-Year-Old Males Is Dependent on Physical Activity at 12 Years and Cumulative Cardiorespiratory Fitness From Puberty to Late Adolescence.

PURPOSE: To evaluate the long-term effect of body composition, physical activity, and cardiorespiratory fitness (CRF) from puberty on arterial health in late adolescent males. METHODS: The cumulative burden of physical activity (measured with accelerometer), CRF (VO2peak0.82), and body composition (body mass index, fat mass, and fat percentage) from puberty to late adolescence (sum of 4 time points from 12 to 18 y) was assessed in 102 males. Additional analysis on the first (T1) and last (T4) time points was performed. Intima-media thickness (IMT), carotid-femoral pulse wave velocity, and augmentation index adjusted to heart rate of 75 beats per minute (bpm) as dependent variables were measured at T4 and analyzed in multivariable regression models adjusted for known risk factors including maturation, blood pressure, and smoking habits. RESULTS: T1 and cumulative body composition measures were independently associated with IMT, while cumulative (ß = -0.011, P = .036) and T4 (ß = -0.0.031, P = .001) CRF revealed independent associations with IMT. Individuals with moderate to vigorous physical activity >60 minutes per day at T1 showed relationship (ß = -1.091, P = .026) with IMT independently of late adolescent physical activity. No significant relationship was present for arterial function. CONCLUSION: Arterial structure in adolescent males is associated with physical activity at 12 years while relationship with CRF can be seen in late adolescence and cumulatively from puberty to late adolescence.

Effect of Half-Marathon Running on Arterial Stiffness and Blood Biomarkers in High-Level and Recreational Male Athletes.

There is no clear understanding about the effect of intensive physical load on arterial stiffness and related biomarkers. The aim of this study was to evaluate the effect of half-marathon running on arterial stiffness and blood biomarkers during post-competitive recovery period in competitive and recreational male athletes. Eleven high-level long-distance runners (27.1 ± 4.8 yrs) and seven recreational athletes (34.3 ± 6.1 yrs), who participated in a half-marathon run were examined. Blood biomarkers and arterial stiffness (SphygmoCor 7.1) were measured at baseline and at 18 to 22 hours after the competition. There were no statistically significant changes between the groups in augmentation index (AIx, AIx@75) or pulse wave velocities at carotid-femoral segment (cfPWV) during recovery period. Between-group comparison did not reveal significant differences in blood pressure and arterial stiffness values at baseline and during recovery period. The change of cfPWV (difference between cfPWV at baseline and cfPWV during post-competitive recovery period) was significantly dependent on race time and sports level of the athlete (high-level or recreational). A significant increase was found in hsCRP, creatine kinase and LDH activity during the post-race period in both groups. No significant changes were found in oxidative stress markers in the groups after the race except for higher diene conjugates level in recreational athletes in comparison with the high-level group during recovery period. Our study results showed that half-marathon competition did not cause any significant changes in arterial stiffness parameters during the recovery period. However, the change in cfPWV was independently associated with half-marathon race time and the athlete's level of training revealing a mild increase of arterial stiffness in high-level athletes and athletes with a faster race time.

Oxidative Stress Parameters and Its Associations With Arterial Stiffness in Competitive Powerlifting Athletes After 12-Week Supervised Strength Training.

Jürgenson, J, Serg, M, Kampus, P, Kals, J, Zagura, M, Viru, M, Zilmer, K, Zilmer, M, Eha, J, and Unt, E. Oxidative stress parameters and its associations with arterial stiffness in competitive powerlifting athletes after 12-week supervised strength training. J Strength Cond Res 33(7): 1816-1822, 2019-Available studies have not revealed a clear understanding of the impact of intensive strength training on arterial stiffness and oxidative stress (OxS) parameters, which may have a significant impact on further cardiovascular health of an athlete. The purpose of this study was to evaluate the effect of a 12-week supervised strength training program (SSTP) on oxidative stress indices and its relationship with arterial stiffness in powerlifting athletes. A total of 19 men (28 ± 6 years) exercised for 12 weeks (4 days per week with intensity 60-90% assessed from 1 repetition maximum, 90-120 minutes per session). Oxidative stress parameters and arterial stiffness (SphygmoCor 7.1) were measured before and after SSTP. The study results showed that total peroxide concentration increased and total antioxidant capacity decreased significantly after SSTP. There were no significant changes in carotid-femoral pulse wave velocity (cfPWV) or in the augmentation index. Correlation analysis revealed that the magnitude of the increase of cfPWV was significantly related to the increase of OxS. The current study demonstrated that a 12-week SSTP in powerlifting athletes produced significant changes in OxS indices, which were positively related to increased aortic stiffness. This novel finding may have significant implications about the effect of OxS on cardiovascular health after high-intensity strength training. Furthermore, strength and conditioningcoaches may have to consider the long-term exercise-induced changes in OxS on an individual level, where increased OxS leads to impaired arterial stiffness and cardiovascular health.

Rapid trabecular bone growth in puberty associated with stiffer arteries in adulthood - longitudinal study on healthy young males.

Longitudinal bone content data from puberty to adulthood was assessed in 102 healthy males and associations with arterial health in adulthood was analysed. Bone growth in puberty was related to arterial stiffening and final bone mineral content to decreased arterial stiffness. Relationships with arterial stiffness were dependent on the studied bone regions. INTRODUCTION: Our aim was to assess the relationships between arterial parameters in adulthood and bone parameters in several locations longitudinally from puberty to 18-years and cross-sectionally at 18-years. METHODS: 102 healthy male data from a 7-year follow-up study was used to analyse total body (TB), femoral neck (FN) and lumbar spine (LS) mineral content and density by DXA, carotid intima-media thickness (cIMT) by ultrasound, carotid-femoral pulse wave velocity (cfPWV) and heart rate adjusted augmentation index (AIxHR75) by applanation tonometry. RESULTS: Linear regression analysis revealed negative associations between LS bone mineral density (BMD) and cfPWV [ß=-1.861, CI -3.589, -0.132, p=0.035] which remained significant [ß=-2.679, CI -4.837, -0.522, p=0.016] after adjustment to smoking, lean mass, weight category, pubertal stage, physical fitness, and activity. For AIxHR75 similar results were present [ß=-0.286, CI -0.553, -0.020, p=0.035], but were dependent on confounders. Analysis on pubertal bone growth speed showed independent positive associations to AIxHR75 between Δ FN bone mineral apparent density (BMAD) [ß=672.50, CI 348.07, 996.93, p<0.001] and Δ LS BMAD [ß=700.40, CI 57.384, 1343.423, p=0.033]. Further analysis combining pubertal bone growth and adulthood BMC revealed that the relationships of AIxHR75 with LS BMC and ΔFN BMAD were independent of each other. CONCLUSION: Trabecular bone regions like lumbar spine and femoral neck, showed stronger relationships with arterial stiffness. Rapid bone growth in puberty is related to arterial stiffening, while final bone mineral content relates to decreased arterial stiffness. These results could indicate that bone metabolism is independently associated with arterial stiffness rather than bone and arteries just having common traits of growth and maturation.

Nebivolol and metoprolol: long-term effects on inflammation and oxidative stress in essential hypertension.

Arterial hypertension is characterised by increased oxidative stress and inflammation, which are associated with further cardiovascular risk. The aim of our study was to investigate the long-term effects of nebivolol and metoprolol succinate on oxidative stress, and on inflammatory and pro-inflammatory markers in patients with hypertension. Eighty patients with never-treated mild-to-moderate essential hypertension, aged 30-65 years, were randomised to a 5 mg daily dose of nebivolol or a 50-100 mg daily dose of metoprolol succinate. Brachial blood pressure, plasma oxidized LDL (oxLDL), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), fibrinogen, intercellular adhesion molecule-1 (ICAM-1), asymmetric dimethylarginine (ADMA), and urine 8-isoprostane levels were measured before and after 1 year of treatment. Nebivolol and metoprolol reduced equally significantly brachial blood pressure. The oxLDL was significantly reduced in both groups (p < 0.01 and for both drugs), but only nebivolol reduced 8-isoprostanes (p = 0.01). In the metoprolol group, change in oxLDL levels correlated with change in systolic blood pressure (r = 0.45; p < 0.01) and pulse pressure (r = 0.47; p < 0.01). Both metoprolol and nebivolol reduced ICAM-1 (p < 0.01). There was no change in IL-6, hsCRP, fibrinogen, or ADMA levels in either group. These data suggest that in long-term antihypertensive treatment both the cardioselective beta blocker metoprolol succinate and the vasodilating beta blocker nebivolol have inflammation-related effects but only nebivolol has a favourable blood pressure-independent effect on oxidative stress.

ß2-microglobulin, a novel biomarker of peripheral arterial disease, independently predicts aortic stiffness in these patients.

Arterial stiffness is a prominent feature of vascular ageing and strongly predicts cardiovascular and total mortality. The ß2-microglobulin, (ß2M) a newly identified biomarker of peripheral arterial disease (PAD), is related to renal insufficiency, inflammatory and neoplastic diseases, but may also play a role in vascular dysfunction. However, the relationship between arterial stiffness and ß2M has not been previously studied in patients with atherosclerosis. In the present study we examined a possible association between ß2M and arterial stiffness in patients with PAD and in healthy subjects. Plasma ß2M levels and parameters of arterial stiffness such as aortic pulse wave velocity (aPWV) and augmentation index (AIx) were measured in 66 patients with PAD and in 66 apparently healthy subjects. Plasma levels of ß2M, aPWV and AIx were significantly increased in patients with PAD compared with controls (1858.1 ± 472.8 vs 1554.5 ± 277.9 µg/L, p < 0.001; 9.9 ± 2.2 m/s vs 7.6 ± 1.6 m/s, p < 0.001; 28 ± 8 vs 14 ± 11%, p < 0.001; respectively). There existed significant correlation between aPWV and ß2M for the patient group (R = 0.47; p < 0.001), but not for the controls (R = 0.14; p = 0.26). In multivariate analysis, ß2M remained independently associated with aPWV, fetuin-A, age and glomerular filtration rate in patients (R(2) = 0.5, p < 0.001). We found no relationship between ß2M and AIx in either group. We demonstrated that among patients with PAD elevated plasma ß2M levels were associated with higher aortic stiffness irrespective of cardiovascular disease risk factors. These data suggest that ß2M may influence the pathogenesis of aortic stiffness in atherosclerosis.

Association between asymmetric dimethylarginine and indices of vascular function in patients with essential hypertension.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and is associated with endothelial dysfunction. The aim of the present study was to investigate the relationship between ADMA, indices of arterial stiffness, endothelial function and carotid artery intima-media thickness (IMT) in hypertension patients. Eighty middle-aged (47 ± 10 years) untreated patients with mild to moderate essential hypertension underwent routine physical examination, pulse wave analysis (PWA), measurement of aortic pulse wave velocity (PWV) and IMT. In PWA, administration of salbutamol and nitroglycerine was used to assess endothelium-dependent (EDV) and endothelium-independent vasodilation, respectively. In univariate analysis, ADMA was correlated with EDV (r = -0.26; p = 0.02) and IMT (r = 0.32; p = 0.007). In multiple regression analysis, ADMA was independently associated with the female gender, EDV, IMT and total cholesterol (R(2) = 0.30; p < 0.001). No correlation was detected between ADMA and augmentation index, central/brachial blood pressure or aortic PWV. In hypertension patients, ADMA is independently correlated with IMT and EDV. Thus, ADMA is a marker of endothelial dysfunction and intima-media thickening in patients with hypertension.

Metabolomic signature of arterial stiffness in male patients with peripheral arterial disease.

Arterial stiffness is an independent determinant of cardiovascular risk and a marker of subclinical organ damage. Metabolomics may facilitate identification of novel low-molecular cardiovascular risk factors. The aim of the present study was to compare metabolic signatures and functional-biochemical characteristics of patients with peripheral arterial disease (PAD) and clinically healthy subjects. We studied 42 men with symptomatic PAD (aged 66±7 years) and 46 healthy men (aged 66±8 years). Aortic pulse wave velocity (aPWV) was assessed by applanation tonometry using the Sphygmocor device. Metabolic profiling was performed with high-performance liquid chromatography and mass spectrometry. Serum oxidized low-density lipoprotein (oxLDL) level was measured by enzyme-linked immunosorbent assay. The aPWV as well as serum levels of lactate, free carnitine and 11 amino acids including tyrosine were higher among the patients with PAD. In contrast, serum levels of pyruvate, citrate, α-ketoglutarate, aconitate and cysteine were higher in the control group. In multiple regression models, aPWV was independently determined by log-tyrosine and log-oxLDL in the patients (R(2)=0.61; P<0.001) and by age, log-pyruvate and log-oxLDL in the controls (R(2)=0.52; P<0.001). Our study describes for the first time significant differences in metabolomic signature of patients with advanced atherosclerosis compared with clinically healthy controls. The aPWV is independently associated with serum levels of tyrosine and oxLDL in the patients with PAD and is related to pyruvate and oxLDL levels in the control group. The measurement of low-molecular metabolites, which are related to changes in vascular phenotypes, may lead to identification of novel vascular risk markers.

Increased carotid artery intima-media thickness and myeloperoxidase level in children with newly diagnosed juvenile idiopathic arthritis.

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is a frequent childhood rheumatic disease characterized by chronic inflammation. The latter has been related to impairment of arterial functional-structural properties, atherogenesis and later cardiovascular events. The objective of this study was to examine intima-media thickness (IMT) and the parameters of arterial stiffness in children with JIA at diagnosis and their correlation with JIA subtype and markers of inflammation and atherosclerosis. METHODS: Thirty-nine newly diagnosed patients with JIA (26 girls; mean age, 13.2 ± 2.6 years) and 27 healthy controls (9 girls; mean age, 13.6 ± 3.4 years) were included in the study. Twelve patients had oligoarthritis, fifteen had extended oligoarthritis and twelve had rheumatoid factor-negative polyarthritis. IMT of the common carotid artery was determined by ultrasonography, carotid-femoral pulse wave velocity (cfPWV) and augmentation index adjusted to a heart rate of 75 beats/min (AIx@75) were determined by applanation tonometry. The serum levels of atherosclerosis-related biomarkers, such as asymmetric dimethylarginine (ADMA), myeloperoxidase (MPO) and adiponectin, were measured by enzyme-linked immunosorbent assay. RESULTS: Mean IMT (0.46 ± 0.04 vs. 0.42 ± 0.04 mm; p = 0.0003) and MPO concentration (115.2 [95% confidence interval {95% CI}, 97.4-136.3] vs. 57.6 [95% CI, 47.1-70.3] ng/ml; p < 0.0001) were higher in the patients with JIA than in the control subjects. The cfPWV, AIx@75 and serum ADMA and adiponectin levels did not significantly differ between the groups and JIA subtypes. Serum adiponectin level correlated negatively with AIx@75 in patients with JIA (r = -0.38; p < 0.05). CONCLUSIONS: Patients with JIA have increased mean IMT and elevated MPO levels at early stages of the disease. AIx@75 was inversely independently associated with adiponectin level in the patients, suggesting that lower adiponectin levels might influence arterial subclinical stiffening in patients with newly diagnosed JIA.

Heat acclimation increases arterial elasticity in young men.

The major physiological adaptations that occur during heat acclimation (HA) are well documented. However, no studies have provided compelling evidence about the effect of HA on arterial elastic properties. The aim of this study was to examine the changes in large artery elasticity (LAE) and small artery elasticity (SAE) concomitant with HA and to determine the potential relationships among changes in arterial elasticity, baseline aerobic fitness level, and improvement in endurance capacity (EC). During 10-day HA, the subjects (n = 21) exercised daily on a treadmill for 110 min at an intensity of 55%-60% of peak oxygen uptake in a climatic chamber preset to 42 °C and 18% relative humidity. EC was tested in the heat before and after HA. Arterial elasticity was assessed by diastolic pulse wave analysis (HDI/Pulse Wave CR-2000) at baseline and after HA. Blood samples were drawn at baseline. After HA, there was a 17% increase in LAE (from 21.19 ± 4.72 mL·mm Hg(-1) × 10 to 24.77 ± 5.91 mL·mm Hg(-1) × 10, p < 0.05) and an 18% increase in SAE (from 9.32 ± 1.76 mL·mm Hg(-1) × 100 to 10.98 ± 1.75 mL·mm Hg(-1) × 100, p < 0.01). EC increased by 86% (from 88.62 ± 27.51 min to 161.95 ± 47.80 min, p < 0.001) as a result of HA. No significant associations were revealed between changes in arterial elasticity parameters and improvement in EC or baseline aerobic fitness level. We demonstrated, for the first time, that HA has a positive impact on the parameters of arterial elasticity. Further investigations are needed to determine the mechanisms underlying these changes and the potential relationships among arterial elasticity, aerobic fitness level, and EC.

Structural and biochemical characteristics of arterial stiffness in patients with atherosclerosis and in healthy subjects.

Arterial stiffness is an independent predictor of vascular morbidity and mortality in patients with atherosclerosis. Angiographic score (ASc) reflects severity of atherosclerosis in patients with peripheral arterial disease (PAD). Osteopontin (OPN) and oxidized low-density lipoprotein (oxLDL) are involved in the pathogenesis of atherosclerosis. The aim of the present study was to evaluate the association between arterial stiffness, ASc, serum OPN and oxLDL in patients with symptomatic PAD, and in clinically healthy subjects. We studied 79 men with symptomatic PAD (mean age 64±7 years) and 84 healthy men (mean age 63±8 years). Calculation of the ASc was based on severity and location of atherosclerotic lesions in the arteries of the lower extremities. Aortic pulse wave velocity (aPWV) was evaluated by applanation tonometry using the Sphygmocor device. Serum OPN and oxLDL levels were determined by enzyme-linked immunosorbent assay. The aPWV (10±2.4 vs. 8.4±1.7 (m s(-1)); P<0.001), OPN (75 (62.3-85.8) vs. 54.8 (47.7-67.9) (ng ml(-1)); P<0.001) and oxLDL (67 (52.5-93.5) vs. 47.5 (37-65.5); P<0.001) were different for the patients and for the controls. In multiple regression models, aPWV was independently determined by ASc, log-OPN, log-oxLDL and estimated glomerular filtration rate in the patients (R2=0.44; P<0.001) and by log-OPN, log-oxLDL, age and heart rate in the controls (R2=0.38; P<0.001). The independent relationship of a PWV with serum levels of OPN and oxLDL in the patients with PAD and in the controls indicates that OPN and oxLDL might influence arterial stiffening in patients with atherosclerosis and in clinically healthy subjects.

Differential effects of nebivolol and metoprolol on central aortic pressure and left ventricular wall thickness.

The aim of this study was to investigate the effects of the vasodilating ß-blocker nebivolol and the cardioselective ß-blocker metoprolol succinate on aortic blood pressure and left ventricular wall thickness. We conducted a randomized, double-blind study on 80 hypertensive patients. The patients received either 5 mg of nebivolol or 50 to 100 mg of metoprolol succinate daily for 1 year. Their heart rate, central and brachial blood pressures, mean arterial pressure, augmentation index, carotid-femoral pulse wave velocity, and left ventricular wall thickness were measured at baseline and at the end of the study. Nebivolol and metoprolol significantly reduced heart rate, brachial blood pressure, and mean arterial pressure to the same degree. However, reductions in central systolic and diastolic blood pressures, central pulse pressure, and left ventricular wall thickness were significant only in the nebivolol group. The change in left ventricular septal wall thickness was significantly correlated with central systolic blood pressure change (r=0.41; P=0.001) and with central pulse pressure change (r=0.32; P=0.01). No significant changes in augmentation index or carotid-femoral pulse wave velocity were detected in either treatment group. This proof-of-principle study provides evidence to suggest that ß-blockers with vasodilating properties may offer advantages over conventional ß-blockers in antihypertensive therapy; however, this remains to be tested in a larger trial.

Association of osteoprotegerin with aortic stiffness in patients with symptomatic peripheral artery disease and in healthy subjects.

BACKGROUND: Arterial stiffening is an independent predictor for cardiovascular mortality. Preliminary studies have shown that arterial calcification may have an impact on increased vascular stiffness. However, there are limited data about the role of calcification inhibitor osteoprotegerin (OPG) as an independent predictor for arterial stiffness in patients with peripheral arterial disease (PAD) and in healthy subjects. The aim of this study was to evaluate the association between OPG and arterial stiffness parameters in patients with PAD and in healthy subjects. METHODS: We studied 69 men with PAD (age 63 + or - 7 years) and 68 healthy subjects (age 54 + or - 8 years). Serum OPG and oxidized low-density lipoprotein (oxLDL) were measured using the enzyme-linked immunosorbent assay method. Radial and aortic pulse wave velocity (aPWV) and augmentation index (AIx) were determined by applanation tonometry. RESULTS: The OPG (5.4 + or - 1.7 vs. 4.4 + or - 1.1 pmol/l; P < 0.001) and aPWV (10.1 + or - 2.5 vs. 7.6 + or - 1.6 m/s; P < 0.001) were different for the patients and for the controls. There was a linear relationship between OPG and aPWV in patients with PAD (R = 0.37; P = 0.003) and in healthy individuals (R = 0.40; P = 0.001). In multiple regression models after adjustment for potential confounders, OPG was independently associated with aPWV in the patients (R(2) = 0.47; P < 0.0001) and in the controls (R(2) = 0.44; P < 0.0001). The AIx or radial PWV was not correlated with OPG for either group. CONCLUSION: The independent association between OPG and aPWV in patients with PAD and in controls suggests that the calcification inhibitor OPG may influence aortic stiffening in atherosclerosis and in clinically healthy subjects.