Session 3 - Lecture 1 - Hypertension & HF Flashcards
1 - SKIP
Hypertension and Heart Failure
2 - Lecture outline
Lecture outline
• Recapitulate basic blood pressure physiology
• Consider the non therapeutic options when initially managing hypertension
• Discuss the antihypertensive therapeutic agents and when and how they are used in managing HT
• Consider some of the evidence that has informed best practise/guidelines
- Review basic pathophysiology of heart failure
- Consider the therapeutic agents (similar to above) that are used in the management of heart failure
- Review some of the evidence that informs this
Make appropriate recommendation for therapeutic agents in management of HT and HF, how they work and important considerations
” 3. standard protocols used in managing hypertensives, particularly primary HT
6. Some of the caveats, recap RAAS”
3 - What is BP?
What is BP?
• Blood pressure provides driving force to perfuse organs with blood (force per unit area acting on arteries) – blood pressure determines tissue perfusion pressure
• Is not uniform throughout the body (remember effects of gravity – typically measure at the level of the heart) and as result of cardiac cycle is cyclical
• Physiologically regulated variable under normal conditions
• MAP = CO X TPR CO = SV X HR
x-axis: 0 Time (sec) 0.8 y-axis: Pressure (mmHg) 80 120 - P diastolic - P systolic - P mean
“Changes in all of us at diff times of the day, & what’s normal for one person is diff for another – changes with age and sex diffs
Cyclical (pulsatile effect) – these things will have been covered in CVS.
Mean arterial pressure = cardiac output x total peripheral resistance.
CO = stroke volume (amount of volume ejected in systole) x heart rate
Schematic between diastolic, systolic, diff between 2 in time-weighted mean is arterial pressure.”
4 - Blood pressure regulation
Blood pressure regulation
• Autonomic sympathetic activity and Renin-angiotensin-aldosterone system
Response mediated by the sympathetic nervous system
Decrease in blood pressure –>
^ Sympathetic activity –>
^ Activation of b1 adrenoceptors on the heart –> ^ Cardiac output
^ Activation of a1 adrenoceptors on smooth muscle –> ^ Increased venous return
^ Peripheral resistance
^ Activation of b1 adrenoceptors on kidney –> ^ Renin
–> Increase in blood pressure
V Renal blood flow –>
V Glomerular filtration rate
–>
Renin –> Angiotensin II –> Aldposterone –> Sodium, water retention –> Blood volume –> Cardiac output –> Increase in blood pressure
Response mediated by the renin-angiotensin-aldosterone system
• Autacoids inc. bradykinin and nitric oxide (action on VSM and endothelium)
Whelan Lippincott
“BP reg. - 2 sorts of major components to target in terms of therapeutic agents – stimulate RAAS angiotensin II for constriction, increase in CO, blood returned to heart, and obvs BP. Couple of other components is some of the Autacoids: locally acting mediators e.g. bradykinin and NO – effects on vascular smooth muscle and endothelium in regulating the tone of the muscle.”
5 - Resistance and increased mean arterial pressure
Resistance and increased mean arterial pressure
Resistance to flow = 8h L / pi r^4
6 - Pathophysiology
Pathophysiology
• Elevated blood pressure (essential/primary/idiopathic) still not completely understood - debated
• Leads to vascular changes inc. remodelling and thickening, hypertrophy
• Increased vasoactive substances inc. ET-1, Nad, angII
• Vascular remodelling as direct result of local salt sensitivity
• Hyperinsulinemia and hyperglycaemia – endothelial dysfunction and reactive oxygen species (ROS) ↓NO
• ….culminating in permanent and maintained medial hypertrophy of vascularture → ↑↑TPR and ↓↓compliance
• End organ damage (renal, peripheral vascular disease, aneurysm, vascular dementia, retinal disease)
• “Hypertensive heart disease” LVH → dilated cardiac failure
• ↑ Morbidity and mortality
“1. So the pathophysiology of HT was discussed of you in CVS last year in terms of primary hypertension i.e. of unknown origin
- We do know that it leads essentially with increased BP to remodelling, thickening of the vascular tissues, arterial sclerosis eventually, hypertrophy of the vasculature
- we get increased vasoactive substances, so endothelium-1, increases in noradrenaline (Nad) and angiotensin II can also be elevated which can contribute to vasoconstriction and ultimately hypertension.
- You can get direct remodelling of the vasculature with some evidence to suggest from local salt sensitivity, so direct salt changes in Na and K can have a direct effect on vascular remodelling.
- Hyperinsulinema and hyperglycamemia again, direct Endothelial effects, cause increases in ROS, interferes in NO production and signalling between cGMP and PKG mechanisms – and ultimately cause vasoconstriction.
- But ultimately a combination in maintained hypertrophy, remodelling of vasculature, causing increased peripheral resistance, decrease in compliance of those vessels and ultimately heart working and pressure needing to be greater to overcome that resistance
- ultimately leading to end organ damage e.g. renal damage, peripheral vascular disease (lecture in CVS), aneurysm, vascular dementia related to hypertensive states and retinal disease.
- Also what we call hypertensive heart disease which ultimately leads to left ventricular hypertrophy, or diseases associated with the CV system itself, leading to dilated cardiac failure – a type of HF talk about a lil more later.
- Ultimately HT will lead to increased morbidity and eventually mortality.”
7 - EU + Norway, Switzerland (and….)
EU + Norway, Switzerland (and….)
y-axis: Prevalence of hypertension (%) 0 10 20 30 40 50
x-axis: Estonia Lithuania Latvia Slovenia Hungary Croatia Slovakia Poland Bulgaria Czech Republic Romania Finland Ireland Portugal Norway Germany Malta Sweden France Cyprus Netherlands Austria Italy Luxembourg Spain UK Switzerland Denmark Greece Belgium
Male Female
Kloss et al. 2015 NFS
“So this is just briefly to show you and you can edit this slide as things change over the next couple of months, I gues we’re doing reasonably well compared to other counteies but prevalence in HT in adults across countries in Europe is a big problem, you can see sex diffs between M and F, I don’t know where there data is from but Females are protected to some extent against HT until they reach menopause and then things level out a bit and they catch the guys up.”
8 - Why treat HT – usually presents asymptomatically
Why treat HT – usually presents asymptomatically
SBP and CHD
x-axis: Usual SBP (mm Hg) 110 120 130 140 150 160 170
y-axis: 0.25 0.50 1.00 2.00 4.00 8.00
SBP and stroke
x-axis: Usual SBP (mm Hg) 110 120 130 140 150 160 170
y-axis: 0.25 0.50 1.00 2.00 4.00 8.00
“So why do we treat HT? This is going to be something, certainly for the GPs amongst you, certainly going to be a challenge for the whole ‘silent killer’ – pt won’t want to take pills bc they feel fine. Well an increase in BP above sort of the relatively normal, so these are relative risk values, an increase above of what’s considered healthy and normal increases risk of CHD, when we’re getting up to 160 which isn’t particularly high, and same with risk of stroke and beyond sort of normal level so we need to treat it – HT is one of the biggest precursors to CVD that are going to kill you.”
9 - Defining HT
Defining HT
• Labile, age, sex and population differences makes defining HT difficult
• “An elevation in blood pressure that is associated with an increase in risk of some harm”
• “Significantly high to cause end organ damage”
• “An elevated blood pressure that treated will do more good than harm”
• NICE suggest that 140/90 mmHg defines hypertension - ≥ 40% population of England
• Reduction in BP – both SBP and DBP reduces CVD risk
• Essential/primary/idiopathic – 90%
secondary
prehypertensive
isolated systolic/diastolic
white coat/clinic - is real phenomenon
“So in terms of defining hypertension, what it is, it’s q difficult bc it’s labile, prone to change, there’s age sex differences, different populations are prone to suffering HT over others, there are particular populations in certain deserts that are almost resistance to HT that makes it q difficult but essentially it’s the elevation of BP associated with causing a recognised harm, maybe end organ damage – or elevated BP that when treated will do more good than harm. So NICE Guidelines suggest systolic over 140 and diastolic over 90 defines HT in most people. >40% of adult English population are said to be hypertensive in this way. So reduction in BP both systolic and diastolic reduces CVD risk, so I suggest in your workbook, I briefly mentioned this, the difference between essential/primary or idiopathic (which is probably more than 90% of people actually) compared to secondary causes, so secondary causes, if you deal with those directly HT goes away. Prehypertensive state is something that you will probably aggressively target: not quite defined as hypertensive but non-pharmacological interventions reduce their risk. Isolated systolic/diastolic where systolic or diastolic is raised but the other isn’t. And white coat/clinic in America is a real phenomenon.”
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