Vascular Ageing and Aerobic Exercise

Impairment of vascular function, in particular endothelial dysfunction and large elastic artery stiffening, represents a major link between ageing and cardiovascular risk. Clinical and experimental studies identified numerous mechanisms responsible for age-related decline of endothelial function and arterial compliance. Since most of these mechanisms are related to oxidative stress or low-grade inflammation, strategies that suppress oxidative stress and inflammation could be effective for preventing age-related changes in arterial function. Indeed, aerobic physical activity, which has been shown to improve intracellular redox balance and mitochondrial health and reduce levels of systemic inflammatory markers, also improves endothelial function and arterial distensibility and reduces risk of cardiovascular diseases. The present paper provides a brief overview of processes underlying age-related changes in arterial function, as well as the mechanisms through which aerobic exercise might prevent or interrupt these processes, and thus attenuate vascular ageing.

Can pulse wave velocity (PWV) alone express arterial stiffness? A neglected tool for vascular function assessment

Arterial stiffness, defined as the rigidity of the arterial wall, is the consequence of vascular aging and is associated with the full spectrum of cardiovascular diseases. Carotid-femoral pulse wave velocity (cf-PWV) is the gold standard method for arterial stiffness evaluation: it measures the velocity of the arterial pulse along the thoracic and abdominal aorta alongside arterial distensibility. Its value rises as stiffness progresses. Cf-PWV is helpful to assess residual cardiovascular risk (CVR) in hypertension (HT). In fact, an increase in pulsatility and arterial stiffness predicts CVR in patients affected by arterial HT, independently of other risk factors. Arterial stiffness can predict cardiovascular events in several other clinical conditions such as heart failure, diabetes, and pulmonary HT. However, cf-PWV has not been yet included in routine clinical practice so far. A possible reason might be its methodological and theoretical limitations (inaccuracy in the traveled distance, intra and interindividual variability, lack of well-defined references values, and age- and blood pressure-independent cutoff). To exceed these limits a strict adherence to guidelines, use of analytical approaches, and possibility of integrating the results with other stiffness examinations are essential approaches.

Association of Circulating Extracellular Matrix Components with Central Hemodynamics and Arterial Distensibility of Peripheral Arteries

<b><i>Background:</i></b> In addition to neuronal and endothelial regulators of vascular tone, the passive mechanical properties of arteries, determined by the molecular structure of extracellular matrices, are the principle modulators of vascular distensibility. Specifically, the association between collagen type IV (Col IV), a constituent of basement membrane, and arterial compliance remains unclear. <b><i>Methods:</i></b> In 31 healthy adult men, radial applanation tonometry and pulse wave analysis were used to assess aortic augmentation index (AIx), aortic-to-radial pulse pressure amplification (PPAmpl), and time to reflection wave. <b><i>Results:</i></b> Plasma Col IV and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) concentrations were correlated with AIx (<i>r</i> = 0.51, <i>p</i> = 0.021 and <i>r</i> = −0.45, <i>p</i> = 0.042, respectively) after adjustment for age and heart rate (HR). Greater matrix metalloproteinase-9 (MMP-9) and TIMP-1 levels were associated with high PPAmpl (<i>r</i> = 0.45 and <i>r</i> = 0.64, respectively) and hence with compliant arteries. Multiple regression analyses revealed that 99% of the variation in PPAmpl was attributable to age, HR, Col IV, TIMP-1, and Col × TIMP-1 interaction (<i>p</i> &#x3c; 0.001). No relations between tonometric variables and levels of MMP-1, -2, and -3; TIMP-2 and -4; fibronectin; glycosaminoglycans; and hydroxyproline were found. <b><i>Conclusion:</i></b> High circulating Col IV level indexes were associated with stiffer peripheral arteries whereas increased MMP-9 and TIMP-1 concentrations were associated with more compliant ones.

Kinetics of Postpartum Mesenteric Artery Structure and Function Relative to Pregnancy and Lactation in Mice

Epidemiological evidence suggests that normal pregnancy in women is associated with decreased cardiovascular risk in later life. Clinical studies have provided evidence that alterations in vascular function and structure are detectable long after delivery. To understand these findings, we examined mesenteric artery reactivity at both early (3 days and 2–4 weeks) and late (12 weeks) postpartum (PP) time points in relation to late pregnancy (LP) and lactation. Vessels from virgin controls, LP, PP, and nursing and non-nursing mothers were tested for responses to phenylephrine (PE), high potassium solutions (high K+), and acetylcholine (ACh). Passive arterial distensibility, vessel dimensions, and collagen and elastin content were evaluated for the studied groups. We observed that (1) there was a significant inhibition of vascular reactivity to PE in LP, 3 days and 2 weeks PP vessels that returned to pre-pregnancy levels at 4 and 12 weeks PP; (2) inhibition of NO production in PP vessels restored PE-induced constriction to pre-pregnancy levels; (3) vasodilator responses to ACh were similar at all PP periods; (4) LP and early PP was associated with a persistent increase in arterial distensibility that correlates with a PP-induced reduction in wall collagen, and regressed to pre-conception levels at 12 weeks PP; (5) vessels from non-nursing PP mice demonstrated an increased PE reactivity, diminished responses to ACh, and reduced distensibility compared to breastfeeding mice. These studies provide a timeframe for mesenteric artery adaptations that occur during pregnancy and extend to the PP period, but which may be modified by PP events.

Predicted Skeletal Muscle Mass and 4-Year Cardiovascular Disease Incidence in Middle-Aged and Elderly Participants of IKARIA Prospective Epidemiological Study: The Mediating Effect of Sex and Cardiometabolic Factors

The sex-specific effect of skeletal muscle mass (SMM) index (SMI) on 4-year first fatal/non-fatal cardiovascular disease (CVD) event in free-of-disease individuals was examined. In 2009, n = 1411 inhabitants (mean age = 64(12)) from Ikaria were selected. Follow-up was performed in 2013. SMI was created to reflect SMM through appendicular skeletal muscle mass (indirectly calculated through formulas) divided by body mass index (BMI). Fifteen and six tenths percent of participants exhibited CVD (19.8% in men/12% in women, p = 0.002). Significant U-shape trends were observed in participants >65 years old and women irrespective to age confirmed through multi-adjusted Cox regression analysis; in age >65 years, Hazard Ratio (HR)(2nd vs. 1st SMI tertile) = 0.80, 95% Confidence Interval (95%CI) (0.45, 0.96) and in women HR(2nd vs. 1st SMI tertile) = 0.71, 95% CI (0.33, 0.95), while, as for the 3rd SMI tertile, no significant trends were observed. Mediation analysis revealed that mediators of the aforementioned associations in men were the arterial distensibility and total testosterone, while, in women, inflammation, insulin resistance, and arterial distensibility. High SMM accompanied by obesity may not guarantee lower CVD risk. Specific cardiometabolic factors seem to explain this need for balance between lean and fat mass.

Arterial Structure and Stiffness Are Altered in Young Adults Born Preterm

Objective: Preterm birth has been associated with changes in arterial structure and function. Association with complications occurring during the neonatal period, including bronchopulmonary dysplasia, on vascular outcomes in adulthood is unknown. Approach and Results: We evaluated a cohort of 86 adults born preterm (below 30 weeks of gestation), compared to 85 adults born term, at a mean age of 23 years. We performed ultrasonographic assessment of the dimensions of the ascending aorta, carotid and brachial arteries, and estimated flow-mediated dilation, carotid-femoral pulse wave velocity, augmentation index corrected for heart rate, and carotid intima-media thickness. All analyses were performed with and without adjustment for potential confounding variables, including height, sex, and body mass index. Ascending aorta diameter in diastole was smaller in the preterm group, but carotid and brachial arteries were similar. Carotid and brachial strain, a marker of arterial distensibility, was smaller in the preterm group, while carotid-femoral pulse wave velocity, was similar between groups, indicating similar aortic stiffness. Carotid intima-media thickness, endothelial function flow-mediated dilation, blood nitrite, and nitrate levels were similar between groups. Individuals with bronchopulmonary dysplasia had lower brachial artery strain suggesting long-term association of this neonatal complication with vascular structure. Diastolic blood pressure was higher in the preterm group and was associated with decreased brachial and carotid distensibility. Conclusions: Young adults born preterm display alterations in arterial distensibility that are associated with a history of bronchopulmonary dysplasia.

Velocity Pulsatility and Arterial Distensibility Along the Internal Carotid Artery

Background Attenuation of velocity pulsatility along the internal carotid artery (ICA) is deemed necessary to protect the microvasculature of the brain. The role of the carotid siphon within the whole ICA trajectory in pulsatility attenuation is still poorly understood. This study aims to assess arterial variances in velocity pulsatility and distensibility over the whole ICA trajectory, including effects of age and sex. Methods and Results We assessed arterial velocity pulsatility and distensibility using flow‐sensitized 2‐dimensional phase‐contrast 3.0 Tesla magnetic resonance imaging in 118 healthy participants. Velocity pulsatility index (vPI=(V max −V min )/V mean ) and arterial distensibility defined as area pulsatility index (A max −A min )/A mean ) were calculated at C1, C3, and C7 segments of the ICA. vPI increased between C1 and C3 (0.85±0.13 versus 0.93±0.13, P <0.001 for averaged right+left ICA) and decreased between C3 and C7 (0.93±0.13 versus 0.84±0.13, P <0.001) with overall no effect (C1–C7). Conversely, the area pulsatility index decreased between C1 and C3 (0.18±0.06 versus 0.14±0.04, P <0.001) and increased between C3 and C7 (0.14±0.04 versus 0.31±0.09, P <0.001). vPI in men is higher than in women and increases with age ( P <0.015). vPI over the carotid siphon declined with age but remained stable over the whole ICA trajectory. Conclusions Along the whole ICA trajectory, vPI increased from extracranial C1 up to the carotid siphon C3 with overall no effect on vPI between extracranial C1 and intracranial C7 segments. This suggests that the bony carotid canal locally limits the arterial distensibility of the ICA, increasing the vPI at C3 which is consequently decreased again over the carotid siphon. In addition, vPI in men is higher and increases with age.

Decreased arterial distensibility and postmeal hyperinsulinemia in young Japanese women with family history of diabetes

IntroductionTo assess vascular function and characterize insulin secretion using a physiological approach in Japanese women with family history of type 2 diabetes (FHD).Research design and methodsStandardized mixed-meal tests were performed with multiple postprandial glucose, insulin and free fatty acids (FFA) measurements over a 30–120 min period in 31 Japanese women aged 21–24 years. Arterial distensibility was assessed as well.ResultsFasting glucose, triglyceride and insulin averaged <90 mg/dL, <60 mg/dL and <5 μU/mL, respectively, and did not differ cross-sectionally between 10 with (FHD+) and 21 without FHD (FHD–). FHD+ showed higher insulin responses not only during the first 30 min (p=0.005) but also during the second hour (60–120 min, p<0,05) in spite of identical postprandial suppression of FFA and identical fasting and postprandial glucose and FFA concentrations, except for higher 60 min FFA in FHD+. Further, FHD+ had decreased arterial distensibility (p=0.003). On multivariate regression analysis, arterial distensibility emerged as the only significant independent predictor of FHD+. Endurance training in FHD+ did not alter decreased arterial distensibility whereas it abolished postprandial hyperinsulinemia.ConclusionsFHD was associated with decreased arterial distensibility and postprandial hyperinsulinemia despite nearly identical postprandial glycemia and postprandial FFA suppression, suggesting that impaired vascular insulin sensitivity may precede glucose and lipid dysmetabolism in normal weight Japanese women aged 22 years.

Abstract P137: Women Experience A Greater Decline In Brachial Artery Distensibility With Age Than Men

Introduction: Brachial artery distensibility is reduced in type 1 diabetes and can predict future coronary artery disease (CAD). Although women generally have reduced cardiovascular risk as compared with men, type 1 diabetes increases cardiovascular risk to a greater degree in women such that their cardiovascular risk matches that in men. Sex differences in arterial distensibility may contribute to the increased cardiovascular risk in women with type 1 diabetes. Hypothesis: We tested the hypothesis that brachial distensibility differed by sex and by diabetes status in a cohort of adults with and without type 1 diabetes. Methods: We measured brachial distensibility via DynaPulse instrument (PulseMetric, San Diego, CA) in 268 adults with type 1 diabetes (mean age 44±9 years) and 373 adults without diabetes (mean age 47 ±8 years) who completed clinical study visits 8±0.89 years apart. A linear mixed model was used to calculate mean brachial distensibility by age at the study visits in men and women by diabetes status. This model was adjusted for age, sex, diabetes status, and visit number. An age group*sex*diabetes interaction was used to calculate least squares means (LSmeans) brachial distensibility and examine trends in each stratum of interest. Results: Brachial distensibility decreases with increasing age (Figure 1). This reduction is greatest for women with type 1 diabetes and smallest for men without diabetes, with decreases from the oldest to youngest age group of 2.6 %/mmHg and 0.98 %/mmHg, respectively. Prior to the age of 40 years, women have better brachial distensibility than men regardless of diabetes status, while men have better brachial distensibility than women beginning in the 40-45 years age group. Conclusions: Women experience a steeper decline in their brachial distensibility than men regardless of diabetes status. Rapid reduction in brachial distensibility may contribute to the increases in cardiovascular risk in women with type 1 diabetes.