Special pops women Flashcards
Structure
Intro Oestrogen Endothelial dysfunction Large elastic artery stiffening Common theme Exercise Exercise and EF Exercise and AS Overall evidence Summary
Intro
• Post menopausal women at increasing risk of CVD. Clearly age is a factor but increase at age 51 relative to men (Statistics Canada, 1999) alludes to something at menopause, such as the decline in ovarian function and oestrogen levels causing increased risk. Declining oestrogen has been linked with cardiovascular alterations such as endothelial dysfunction and large elastic artery stiffening. This can be postulated to be a result of oxidative stress amongst other things. Exercise has been linked with reduced oxidative stress and improved endothelial function. This essay examines whether exercise can potentially attenuate these changes and have a positive effect ton cardiovascular physiology in PMW.
Oestrogen
- Oestrogen appears to have a central role in the development of CVD. Early menopause (<=50years) having greater risk of CVD mortality (1.27RR) Lobo 2007, alludes that oestrogen is an important RF from CVS.
- oestrogen is also associated with
- Lowers LDLs
- Lower atherosclerotic Lesions
- Increased antioxidant/ anti-inflammatory effects
- Decreases constricting factors
- Increases NO
- Regulatory role of Lymphocytes and macrophages
- Decreases SN
- Decreases infarct size and damage
- Deficiency at menopause has been linked with:
- Less known about the consequences in FHA (functional hypothalamic amerrhea), focuses on PMW
- Pertubationn in autonomic function
- Activation of RAAS - Hypertension
- Increases cholesterol
- ED and AS
Endothelial dys
3.1 Edothelial dysfunction
• Consequence of and mediator to atherosclerosis development
• Impaired production and release of NO
• ED and NO bioavailability Lead to Vasoconstriction, SM thickening, platelet agg and thrombosis, lipid deposition (Park et al 2015)
• Unknown why but may be due to:
o Estrogen deficiency – lack of estrogen receptor signalling
o Oxiditive stress,
Soak up NO and lower levels – cause EF
o increased because:
Oestorgen is an antioxidant
eNOS uncoupling - production of ROS instead of NO
• TNF-a and inflammation – show to be upreg in rats with ovariectomy.
o decrease No production and scavenge aswel as other negatives such as timulate acute phase reactants, leukocyte accumulation in the vascular wall
Large elastic artery stiffening
- Compliance = ability to expand and recoil with cardiac pulsation and relaxation
- Greater in non-HT users
- Menopause is an independent factor causing augmentation of age related increase in arterial stiffess in the early post-menopausal transition /Diminished with age anyway (collagen and elastin in aorta)
- Associated with CV disease, hypertension and HF
- Diminishes Windkessel effect (storing of some ejected blood from heart from compliant arteriaes in aorta) disruption of steady flow and dampening effect of fluctuations in BP
- Consequences of relflected waves, as BP waves (generated by sytole) propagates through the arterial tree they are met by increasing vascular resistance which causes reflected backwards waves of pressure which summate and travel towards the heart.
- In stiff vessels these arrive faster during systole instead of diastole, and increase the pressure of which the heart has to pump againsts, increasing SBP
- The peak wave velocity is subsequently an independent RF for CVD
- Potentially due to:
- Structural alterations (Oestrogen increase elastin and inhibt collagen synth in animals, prevent SM prolif)
- Functional changes is SM cell tone (related to FMD and NO)
- Oxiditive stress
- Superoxide anion increases collagen deposition and accelerates elastin breakdown
Exercise reverse
• Common theme seems to be oxidative stress
• Increase free radicals with aging and with oestrogen deficiency
• Chronic increase causes cellular damage
• Exercise can reduce oxidative stress and other potentially detrimental factors e.g. TNFa, thickening etc. Santos-Parker et al. 2014
• E.g. Regular exercise training is associated with improved endothelial function, particularly in those with CV risk
• Reduction in inflammatory/hemostatic biomarks, blood pressure, lipid markers, BMI and HBA1c
• All explained a proportion of the observed inverse association
Mora et al 2007
• Exercise improves arterial function, through various means including reduction of oxidative damage/ inflammation,
• Could this attenuate damage?
Exerceise and EF
- Can exercise improve EF?
- One study found that FMD can be improved after 12 weeks of mod-vig exercise (4day/week), only in those with greatest impairment, not overall. Only 24 sededntary PMW.
- Lack of control
- Swift et al 2014
- Aerobic exercise for 12 weeks (Moreau et al 2013)
- No improvement in FMD in 12 weeks of exercise women, small numbers n=36 randomised to 3 groups, walk 40-45 mins/day 5-7days per week
- Habitual (>5 years) endurance training also shown to have no effect on BA FMD but does in similar age males (Pierce et al 2011)
- Despite similar aerobic capacity
- Cross sectional
- Why?
- Increased oxidative stress?
- Why does this mean exercise doesn’t help?
- Increased oxidative stress appears to mitigate the beneficial effects of exercise training, unclear as other anitoxidants do help?
- Can exercise with antioxidants improve EF?
- Ascorbic acid increases FMD in PMW
- Suggests oxidative stress is impairing FMD
- Exercise no effect
- Moreau et al 2013
- Can exercise with oestrogen improve this (lead on as oestrogen is an antioxidant)?
- Oestrogen and exercise improve FMD
- Ostrogen alone improves FMD
- Ostrogen + exercise improved FMD even more
- Moreau et al 2013
- May be more vig exercise than walking needed?
Exercise and AS
- Can exercise with antioxidants improve arterial stiffness?
- potentially decrease PWV and hypertension from reflective waves
- Tanaka et al 1998
- Decreased aortic PWV, cross sectional looking at 53 healthy females
- Dispite the limitations of cross sectional Numerous studies have shown endurance exercise associated with attenuated age-associated increases in arterial stiffness in sedentary PMW (Moreau and Hildreth 2014)
- So is oestrogen
- exercise results in Results in decreased deposition of collagement and fragmentation of elastin
Overall exercise
- Overall physical activity (of which exercise is a form of) lowers mortality in females
- Largescale prospective evidence, women >45years
- Reduction in inflammatory/hemostatic biomarks, blood pressure, lipid markers, BMI and HBA1c
- All explained a proportion of the observed inverse association
- Mora et al 2007
- Unknown what type, vol, intensity to optiomise, may not be as efficient strategy to tackle vascular probs as with men
