The role of physical activity, cardiorespiratory fitness and exercise on the autonomic and arterial systems of healthy adolescents

Cardiovascular diseases (CVD) are the leading cause of death worldwide and the atherosclerotic process that precedes CVD starts during childhood. Physical activity (PA), cardiorespiratory fitness (CRF) and exercise are well known as preventive strategies for CVD. One possible mechanism for such prevention is the role of PA, CRF and exercise on the arterial and autonomic systems. The aim of this thesis was to investigate using observational and experimental studies the role of PA, CRF and exercise on the autonomic and arterial systems of healthy adolescents. Chapter 4 systematically reviewed observational cross-sectional studies and provided level one evidence for a significant and positive association between resting parasympathetic function and moderate-to-vigorous PA in youth. Chapter 4 also indicated that gaps exist in the literature such as the associations between PA intensities, CRF and heart rate variability (HRV). These findings were furthered in Chapter 5 which showed that vigorous PA (VPA) and moderate PA (MPA) were positively related with HRV at rest and cardiac autonomic recovery following exercise in adolescents. In Chapter 6 a high-fat meal was used aiming to increase CVD risk in the postprandial state, and it was demonstrated that PA levels and CRF are not significantly associated with postprandial HRV and arterial stiffness in adolescents. Aiming to investigate possible associations between the vascular and autonomic system, measures of baroreflex sensitivity (BRS) were introduced. Chapter 7 showed that BRS and its autonomic and vascular components present a between-day coefficient of variation lower than 20% whilst within day coefficient of variations were lower than 34% in adolescents. In Chapter 8 acutely following high- and moderate-intensity interval exercise a decrease in blood pressure was observed concomitantly with decreases in BRS. This was mainly mediated by decreases in the autonomic modulation, and the duration of the decreases in blood pressure was higher following high-intensity interval exercise. Chapter 9 extended these findings by demonstrating that the changes in BRS following the ingestion of glucose was not altered by the high or moderate-intensity exercise performed before glucose ingestion. Chapter 10 showed that following four weeks of high-intensity exercise interval training no improvements were observed in BRS and its autonomic and vascular components at rest or acutely following exercise. Collectively, the present thesis contributes significantly to the literature by providing novel evidence in healthy adolescents on the role of PA intensities, CRF and exercise on the arterial and autonomic systems at rest, acutely following exercise and in the postprandial state. The results gathered in this thesis indicate potential of the autonomic and vascular function as targets of CVD risk reduction in youth.Coordenação de aperfeiçoamento de pessoal de nível superior - CAPES. Brazi

Spontaneous baroreflex sensitivity and its association with age, sex, obesity indices and hypertension:a population study

BACKGROUND: Low baroreflex sensitivity (BRS) is an established risk factor for cardiovascular disorders. We investigated determinants of BRS in a large sample from general population. METHODS: In a population-based study (n=901) data were collected on BRS, arm cuff blood pressure (BP) and obesity indices including body mass index (BMI), waist-to-hip ratio (WHR), waist circumference and percentage body fat (%BF). BRS was calculated by spectral analysis software based on continuously recorded spontaneous fluctuations in beat-to-beat finger BP for 10 to 15 minutes. Correlations and multivariable regression analyses were used to test associations of age, sex, obesity indices and hypertension with BRS while considering effects of lifestyle factors (smoking, alcohol consumption and physical activity). RESULTS: In multivariable analysis, age, sex, %BF, and hypertension were independently associated with BRS. BRS decreased with -0.10 (95% confidence interval [CI]: -0.15 to -0.06) ms/mmHg with each year of increase in age. Women had -1.55 (95% CI: -2.28 to -0.73) ms/mmHg lower mean BRS than men. The effects of %BF (per 10% increase) and hypertension on BRS were -0.55 (95% CI: -0.97 to -0.13) ms/mmHg and -1.23 (95% CI: -1.92 to -0.46) ms/mmHg, respectively. There was no evidence of associations between BRS and lifestyle factors. Age, age 2, sex, and their interactions plus %BF and hypertension contributed 16.9% of total variance of BRS. CONCLUSIONS: In this large general population study, we confirm prior findings that age and sex are important factors associated with BRS and find %BF is more strongly related to less favorable BRS levels than BMI

Heart rate variability in young adults - Reference values and associations with cardiometabolic risk factors and vascular properties. The Cardiovascular Risk in Young Finns Study.

Background: The function of the autonomic nervous system (ANS) can be evaluated with heart rate variability (HRV). Decreased HRV is associated with aging, the male sex, increased heart rate, and overall increased cardiometabolic risk. It has been hypothesized that early atherosclerotic vascular changes and ANS function are related. Aims: The aims were to assess reference values on HRV in young adults, and examine associations with HRV and cardiometabolic risk factors and metabolic syndrome (MetS) and to study relations between HRV and ultrasonographically measured vascular properties. Participants and methods: The present thesis is part of the Cardiovascular Risk in Young Finns Study. The thesis is based on the follow-up study in 2001, when the study individuals were 24-39 years of age. HRV data were available on 1 956 individuals. Results: HRV was inversely associated with age and heart rate (for all p<0.001). Highfrequency HRV (HF) was higher, and low-frequency HRV (LF) lower in women than men (p<0.0001 for both). MetS was associated with 11% decreased HF and 12% increased LF/HF-ratio in women, and 8% decreased HF and 4% increased LF/HF-ratio in men. Carotid artery distensibility was independently associated with HF and total HRV (for both p<0.05). Conclusions: The reference values in young adults were generated. Decreased HRV was associated with age, the male sex and increased heart rate. Women had higher HF and lower LF variability than men. MetS was related to decrease in HRV. The observed associations between carotid elasticity and HRV, supports the hypothesis that reduction in carotid elasticity may lead to decrease in autonomic cardiac control.Sydämen sykevaihtelu nuorilla aikuisilla – viitearvot ja yhteys sydän- ja verisuonitautien riskitekijöihin sekä varhaisiin valtimomuutoksiin Tausta: Autonomisen hermoston toimintaa voidaan arvioida mittaamalla sydämen syketaajuudessa tapahtuvaa jaksoittaista vaihtelua, sydämen sykevaihtelua. Vähentynyt sydämen sykevaihtelu on sydän- ja verisuonitautien itsenäinen riskitekijä. Sykevaihtelun väheneminen liittyy ikääntymiseen, miessukupuoleen ja kiihtyneeseen sydämen syketaajuuteen sekä useisiin valtimotaudin riskitekijöihin. Varhaisten valtimotautimuutosten sekä autonomisen hermoston toiminnan välillä on aiemmin esitetty olevan yhteys, jota voidaan tutkia sykevaihtelun ja ultraäänellä mitattujen varhaisten valtimomuuttujien avulla. Tavoite: Tutkimuksen tavoitteena oli luoda sykevaihtelun viitearvot nuorille aikuisille sekä tutkia sykevaihtelun yhteyttä sydän- ja verisuonitautien riskitekijöihin ja metaboliseen oireyhtymään sekä selvittää onko varhaisilla valtimomuutoksilla yhteyttä sydämen autonomiseen säätelyyn. Menetelmät: Väitöskirjatutkimus on osa Lasten Sepelvaltimotaudin Riskitekijät – tutkimusta ja perustuu vuonna 2001 toteutettuun seurantatutkimukseen, jolloin tutkittavat olivat iältään 24–39 vuotta. Tutkimukseen oli käytettävissä 1 956 tutkimushenkilön sykevaihtelumittaukset. Tulokset: Kaikki sykevaihtelun muuttujat olivat yhteydessä tutkittavien ikään ja syketaajuuteen (molemmilla p<0.001). Naisilla korkeataajuuksinen sykevaihtelu oli miehiä runsaampaa (p<0.0001) ja matalataajuuksinen sykevaihtelu vähäisempää (p<0.0001). Metaboliseen oireyhtymään liittyi vähentynyt matalataajuuksinen sykevaihtelu (-11% naisilla ja -8% miehillä). Kaulavaltimon elastisuus oli itsenäisesti yhteydessä sydämen sykevaihteluun (p<0.05). Johtopäätökset: Tutkimuksessa luotiin sykevaihtelun viitearvot terveille aikuisille. Sykevaihteluun vaikuttivat voimakkaimmin ikä, sukupuoli sekä syketaajuus. Metaboliseen oireyhtymään liittyi merkittävästi vähentynyt sykevaihtelu. Valtimoiden seinämän jäykistyminen saattaa olla yksi mekanismi sydämen autonomisen säätelyn muutosten taustalla.Siirretty Doriast

Placental function, body composition and cardiovascular autonomic function

Hypertension is an important modifiable risk factor for cardiovascular disease. An important recent advancement in hypertension research is an understanding that hypertension often may have a developmental origin. Birthweight is associated with hypertension across the lifespan and adult cardiovascular disease, such that those at both ends of the spectrum are at increased risk. Nonetheless, birthweight is a crude surrogate of fetal growth and it may be that quantification of body composition, may more accurately identify the “at risk” individual. A causative mechanism linking birthweight and cardiovascular risk is yet to be identified but may involve changes to the structure and function of organs including the placenta which may impair development and predispose individuals to later cardiovascular disease. The aims of this thesis were to investigate the associations between placental function, body composition and cardiovascular autonomic function. Studies outlines in this thesis indicate different mechanism control fat mass and fat free mass in the newborn and that placental weight partly mediates the association of maternal factors with newborn body composition. While low birthweight has previously been shown to be associated altered autonomic function in the infant our studies suggests that body fatness may provide information beyond that obtained from birthweight assessment alone. Previous studies have shown altered blood pressure control in those born preterm, our studies found altered cardiovascular outcomes even in the late preterm newborn. Assessment of body composition in children and adolescents at rest and in response to an exercise test suggests worsening of autonomic control due to adiposity and may develop over time during childhood and adolescence. Collectively, these results emphasise the implications of altered in-utero and early life exposures on cardiovascular outcomes

Clinical studies of the renin-angiotensin-aldosterone system and cardiac autonomic regulation in man

The work embodied in this thesis was designed to explore the interaction between the renin -angiotensin -aldosterone system (RAAS) and the autonomic nervous system. It was stimulated by the observations that the neurohormonal suppression of the RAAS by ACE inhibitors in chronic heart failure (CHF) is inadequate, and that high residual levels of circulating aldosterone have been shown to have detrimental autonomic modulating effects independent of angiotensin II in experimental models.The effects of aldosterone blockade with spironolactone therapy were examined in CHF patients already established on ACE inhibitors. It was observed that spironolactone has beneficial parasympathomimetic properties, improving heart rate variability and reducing heart rate, particularly during the early morning hours of the day when ACTH -induced aldosterone secretion is maximal. The interaction between the RAAS and the parasympathetic tone was explored further in a series of normal volunteer studies. Although the effects of ACE inhibitors are well recognised, not much is known about the parasympathomimetic properties of direct angiotensin II or aldosterone receptor antagonism. In this thesis, it was demonstrated that losartan, an angiotensin II receptor antagonist, and enalapril, an ACE inhibitor, were equally effective in improving the vagally-mediated baroreflex response in salt depleted normotensive subjects. It was also demonstrated that direct intravenous aldosterone administration impaired the baroreflex response to vasopressor agents in healthy subjects.The observed vagomimetic effects of aldosterone blockade may have important therapeutic implications, suggesting the possibility that spironolactone may have anti -ischaemic or anti -arrhythmic properties. However, aldosterone blockade did not appear to have any significant impact on either autonomic tone or ischaemic events when administered to patients with ischaemic heart disease but preserved LV function. The reasons for the latter remain unclear but may reflect differences in disease -state (less neurohormonal activation, and a larger proportion of these patients was established on beta -blockers -which may influence autonomic tone - and only a minority was taking concomitant ACE inhibitors, compared to the CHF cohort). In CHF however, spironolactone was shown to improve QT dispersion, a surrogate marker of arrhythmic activity and sudden cardiac death. Mechanisms in which aldosterone may contribute towards dispersion of the QT intervals on the electrocardiogram are probably multifactorial. Aldosterone increases cardiac afterload (by increasing vascular tone and potentiating vascular smooth muscle hypertrophy) and it is demonstrated that cardiac afterload would increase QT dispersion through mechano- electrical feedback. Vagal tone modulation itself however did not contribute towards QT dispersion.These studies demonstrate how inextricably linked the RAAS and the autonomic nervous system is. In particular, the detrimental autonomic effects of aldosterone in CHF have been highlighted. The findings of these studies highlight possible mechanisms and provide valuable insights as to why further therapeutic mileage is gained by the addition of an aldosterone antagonist in CHF patients who have already been established on ACE inhibitors