Hypertension

Hypertension handout

Rob Hunter

2025-02-18

These lecture notes accompany the KCP Lecture on Hypertension (2025). They are best viewed on a full-size screen on a computer or tablet (or else the margin notes may disappear).

They are an adjunct to the lecture and may not make complete sense in isolation.

You definitely don’t need to know all this in great detail at this stage. Hypertension is a topic that you will return to many times throughout your medical education. So the intention is to convey the underlying core principles. Much of the extra detail provided in these notes is really to signpost sources of additional information that may be useful now and in the future.



Learning objectives



Take-home messages



What is blood pressure?

The Rev Stephen Hales inserted a brass tube via a goose trachea into horse’s neck to make the first recorded measurement of blood pressure. He did this in 1733: 300 yrs ago and c. 100 yrs after William Harvey. Today, we can measure invasive blood pressure in similar fashion by inserting arterial lines in the setting of intensive or peri-operative care…

…but we usually measure blood pressure non-invasively using a cuff sphygmomanometer. These may be operated manually (where cuff used to occlude blood flow and we listen to sound of blood flow returning) or automated using an oscillometric device.


Units

Pressure = force per unit area, so SI units are Pa = Nm-2. Because of how blood pressure was measured historically, blood pressure is expressed in mmHg1 To put these units into context: 1 bar = 750 mmHg = 100kPa = atmospheric pressure = 1000 cmH2O; sABP = 150 mmHg = 0.2 bar = 200 cmH2O; mains water pressure = 2 - 4 bar; typical domestic hot water system = 1 – 2 bar; car tyres = 2 bar; bike tyres = 5 bar… …so blood pressure is around 1/10th of the sorts of pressures we are used to in daily life: the force required to oppose gravity and sustain a vertical column of mercury.


Terminology

When we say ‘BP is 280/160 mmHg’ – what exactly does this mean? This is slightly sloppy terminology. We should really say 'systemic arterial blood pressure' to differentiate from the pulmonary arterial or systemic venous circulations.

We usually measure systolic (when the heart is pumping) and diastolic (when the heart is relaxed). Sometimes we then calculate the mean value throughout the cardiac cycle.



Why do we have a blood pressure?

We have evolved a reasonably high blood pressure for a reason. Not all living things have such a high blood pressure. But why? What advantage does this confer?

Clearly, in part related to metabolic rate:

Figure adapted from Cardiovascular Physiology of Dinosaurs, Seymour (2016).

Remember Ohm’s law: \(V = IR\)? Darcy’s2 Darcy was French civil engineer, studying water flow through gravel beds of Dijon in 1850s. law broadly analogous if talking about pressure and flow in fluids: \(\Delta P = QR\). Or rearranged: \(Q = \frac{\Delta P}{R}\). The flow of fluid through a vessel is proportional to the pressure gradient, \(\Delta P\). So one3 More completely, the evolution of highish blood pressure was driven by: 1) increased metabolic rate (and endothermy) = need for higher O2 delivery = higher Q; 2) reduction in capillary size (so can have increased density and better O2 delivery) = higher R …therefore \(\Delta P\) must also increase; 3) required development of a parallel pulmonary circulation (otherwise tissue oedema limiting gas exchange); 4) …and also requirement to overcome gravity key driver was the evolutionary advantage of higher metabolic rate (high in mammals – can run; higher in birds – can fly!). For higher \(Q\), you need need higher \(\Delta P\).


But is that the whole story? What if we look now only in mammals:

Figure adapted from Cardiovascular Physiology of Dinosaurs, Seymour (2016).

There are two striking observations:

  1. the Giraffe (so sometimes gravity is important - but only rarely)
  2. the rest are remarkably similar!

So blood pressure cannot simply be maintained high because of increased TPR as ABP is roughly the same despite big variation in CO and TPR. So why is ABP so remarkably constant?

There are three main answers as to why mammals have high ABP:

  1. allows dynamic distribution of blood on demand through parallel vascular beds; so critical organ perfusion doesn’t fall off when we eat a meal or go running (turning on the kitchen taps when in the shower analogy)

  2. to sustain glomerular filtration pressures

  3. keeps cardiac afterload relatively constant



How is blood pressure controlled?

Consider the circulatory system:

The key components are:


Within any vascular bed, flow is determined by the resistance of that bed: \(Q = \frac{\Delta P}{R}\). Therefore the arterioles in that bed can control flow through it.

This system only works if pressure is maintained. Consider septic or anaphylactic shock: like everybody turning on the taps in the kitchen and bathroom when you are trying to have a shower. (We discuss a real case like this in the lecture.)


The pressure in the whole system - blood pressure - is determined by flow into the arterial tree (cardiac output, CO) and the total peripheral resistance (TPR - sometimes termed systemic vascular resistance, SVR): \(ABP = CO \times TBP\).

This is a really important concept, that we returned to several times during the lecture. All causes of high (or low) blood pressure act by changing cardiac output or peripheral resistance. As CO is tightly controlled, the main variable that changes in most circumstances is TPR. All treatments for high blood pressure act by reducing peripheral resistance.6 The other really important factor is total body NaCl content, regulated by renal NaCl excretion. For reasons that are quite complicated, when total body NaCl increases, this manifests as increased TPR. The reason that diuretics lower blood pressure in the long term is that they reduce TPR. Google ‘Guyton’s theory of whole-body autoregulation’ if you are interested in reading more about this.


ABP so important that it is a sensed variable. There are pressure sensors in large arteries and kidneys, triggering effector responses through sympathetic nervous system, RAAS and urinary salt/water output. They key controllers of blood pressure are:

  1. the sympathetic nervous system (for short-term control) - stimulated by baroreceptors in the carotids
  2. the renin-angiotensin-aldosterone system, RAAS - stimulated by receptors in the kidney
  3. total body NaCl7 There is a wealth of strong evidence for this. One interesting example is in patients on long-term dialysis therapy. Removing NaCl on dialysis can be used to lower blood pressure., set by excretion through the kidneys (long-term control)


This is a useful model to keep in your head when thinking about causes of high blood pressure and treatments for high blood pressure. To keep things simple, we can re-draw as:



Causes of high blood pressure

High blood pressure is known as hypertension; we will define this more rigorously below.

Causes of hypertension may be classified as 'secondary' when there is a clear precipitating cause (5 - 10%) or 'essential' or ‘primary’ when there is not (90 - 95%). The term ‘essential’ is a historical misnomer: it was once thought that blood pressure had to increase in old age to maintain tissue perfusion.


Secondary hypertension

The main causes of secondary hypertension are:



Primary hypertension

Blood pressure is a continuous trait. The known contributors to high blood pressure are:



Hypertension

Hypertension was recognised as a disease before we could measure blood pressure or treat high ABP. The Ebers papyrus (ancient Egyptian c. 1500 BCE) described relationship between stiff pulse and heart / brain disease. FDR died from hypertension in 1945: not dissimilar from the case we discussed during the lecture.


Definition of hypertension

But what is hypertension? How high is too high? Hypertension is a blood pressure that is high enough to cause disease (or even better a blood pressure for which treatment with anti-hypertensive therapy is likely to do more good than harm.13 Actually, overall cardiovascular risk score more important in determining outcome than ABP per se – so perhaps we should base treatment decisions on that? This is accepted to be 140/90 mmHg in most guidelines.

Where does 140/90 come from? 140/90 initially from the HOT trial and substantiated in many subsequent RCTs and meta-analyses. Lower limit of benefit still a matter of debate. The SPRINT trial demonstrated benefits of targeting ABP < 120 mmHg systolic14 In the 1970s, diastolic blood pressure was considered the most appropriate target. There has since been a growing recognition of the importance of systolic blood pressure. In ageing, as the large arteries stiffen, there is a progressive rise in systolic and fall in diastolic blood pressure; hence why systolic now preferred as a more reliable marker of cardiovascular risk. But probably no lower limit; therefore limited only by side-effects. In general, CVS risk is elevated at ABP > 115/75. Lowering by 10/5 mmHg causes a 30 – 40% relative risk reduction in the risk of stroke or MI.


Consequences of hypertension

Hypertension causes:


Accordingly, treatment to lower blood pressure leads to reduced risk of cardiovascular disease:

Figure from Ettehad, Lancet 2016.16 Meta-analysis of RCTs in over 600,000 adults. Risk reduction in proportion to ABP lowering. Meta-regression plot: each circle represents an RCT.


Prevalence of hypertension

Hypertension is a global problem. 1 billion adults worldwide have HTN. Is the single most important leading cause of death worldwide (more than smoking and diabetes). 50% of adults with HTN are unaware that they have it; 80% have suboptimal ABP control.17 See WHO report and WHO factsheet.

There is geographical variation and also evidence that HTN varies by race within countries – e.g. higher in Black Americans than in White and Hispanic Americans:

Figure from Mills, Nat Rev Nephol 2020.


Why is hypertension more prevalent in Black Americans? No strong evidence that genetic differences explain higher prevalence of HTN in Black individuals; therefore socioeconomic factors are likely to predominate.18 UK observational data showed that anti-hypertensive initiation was similar across ethnic groups but that subsequent ABP control was poorer, medication adherence lower and discontinuation higher in individuals with Black African / Carribean family origin.

Contributing factors could include:


Treating hypertension

Hypertension may be treated with:


Lifestyle measures are super important. Smoking cessation probably reduces blood pressure per se and is also independently important for cardiovascular risk.19 Tobacco activates sympathetic nervous system - see WHO report.

Drugs act predominantly by reducing TPR. New drugs are being trialled even these days – e.g. aldosterone synthase inhibitors and siRNA against angiotensiongen.

Mechanical sympatholytics were an early, historical treatment - now abandoned. A similar approach now seeing a resurgence in the form of renal denervation.


How do deploy all these options? See BMJ infographic on NICE guidance:


…or a simplified version:

:scale 50%

Important to emphasise individualizing therapy based on whole patient / patient preferences etc.

This treatment algorithm is unusual in medicine in that it stratifies treatment by ethnicity (as well as by age and diabetes status). Why is that? The concept of ‘low renin’ (ACEi-resistant) HTN in Black individuals stems from historic, poor quality studies and secondary analyses of ALLHAT. This is increasingly controversial because of i) poor quality evidence; ii) problems defining race of any one individual; iii) potential for introducing health inequalities – e.g. Black patients with CKD may miss out on ACEi/ARB even though we know these work well at preventing progressive CKD from AASK. Observational data20 e.g. here & here that actually response to RASi no different in different ethnic groups. They also show no difference in ABP response by age until get to very old: CCB better than ACEi/ARB in over 75s.

The preference for CCB / thiazide in Black individuals is also contained in other international guidelines (JNC8 2014, ACA/AHA 2017, ESC 2018). The preference for CCB in older patients is peculiar to UK NICE guidance. It seems likely that in future guidelines could be simplified to permit use of any of the three major drug classes in all patients. Indeed WHO Guidelines (2021) recommend first-line treatment with any of thiazide, CCB or ACEi/ARB.


Further detail on the molecular mechanisms regulating vascular tone:

Post-ganglionic fibres release noradrenaline – then acts on alpha / beta adrenoceptors.21 \(\alpha 1\) = vasoconstriction; \(\beta 1\) = tachycardia; \(\beta 2\) = vasodilatation, bronchodilatation

All vascular SmM contraction is driven by intracellular calcium.22 Ca2+ binds calmodulin > MLCK > myosin activation

Calcium may enter: