Sunday, December 23, 2012

Hypertension

Summary
 
When you get your blood pressure taken systolic blood pressure is the higher number and diastolic blood pressure is the lower number.  Two other measurements can be taken from systolic and diastolic blood pressure: mean arterial pressure is one third systolic plus two thirds diastolic; and pulse pressure is systolic minus diastolic.
 
Cardiac output (which is equalled to heart rate multiplied by stroke volume (stroke volume is affected by blood volume)), arterial width/peripheral resistance and arterial stiffness are some main factors that could affect blood pressure.
 
Salt reduces blood pressure, but not much or in amounts that would suggest that high salt diet causes hypertension or low salt would reverse it.  Restricting salt increases activation of the renin-angiotensin-aldosterone system (RAAS) and noradrenaline, which has some undesirable effects such as increasing insulin resistance and oxidative stress.
 
Obesity, insulin resistance, endothelial dysfunction, atherosclerosis and poor kidney function are some of the mechanisms of hypertension and tend to affect blood pressure by increasing the activity of the sympathetic nervous system (SNS), the renin-angiotensin-aldosterone system and arterial stiffness.
 
 
Some Strategies for Hypertension
 
This is for informational purposes only and is not meant to diagnose or treat any medical condition.
 
Obesity
 
Obesity, even without insulin resistance, is one of the major factors in hypertension.  See Obesity
 
Insulin Resistance and Type 2 Diabetes
 
It’s estimated that 50% of people with hypertension are insulin resistant [1].  Insulin resistance increases SNS and RAAS activity and impairs endothelial function, and type 2 diabetes is the major cause of kidney failure [2].  See What Causes Insulin Resistance? Part VII
 
Cardiovascular Disease
 
Endothelial dysfunction and atherosclerosis can increase arterial stiffness and blood pressure (particularly systolic).  See Cardiovascular Disease
 
Stress/Anxiety
 
Psychological stress/anxiety can definitely increase blood pressure in the short term and is a factor in white coat hypertension, but it’s debatable as to whether it causes hypertension.  That being said, meditation reduces blood pressure in people with mild hypertension [3]
 
Nutrients
 
Reducing salt does reduce blood pressure, but not by much, although more so in people with hypertension, poor kidney function and African Americans.  Don’t expect that reducing salt will normalise your blood pressure.  Most sources of salt are in processed foods, take-away foods, restaurants and added salt.  Whole foods are usually very low in salt*
 
Potassium supplementation may be more effective than sodium at reducing blood pressure.  However, it also has a fairly minor effect and seems to only be effective in those with hypertension.  Potassium also doesn’t seem to increase SNS and RAAS activity like salt restriction does [4].  Although another meta-analysis found no benefit [5]
 
Sun exposure is associated with lower blood pressure [6].  Vitamin D inhibits the RAAS [7], but supplementing vitamin D may not as sunlight increases nitric oxide [6]
 
Vitamin K2 may be helpful as it prevents calcification of arteries

Sunday, December 16, 2012

Mechanisms of Hypertension

Overweight/Obese
 
Overweight/obesity is associated with hypertension and most people with hypertension are also overweight.  Weight gain increases blood pressure and weight loss reduces it [1].  The interaction of weight and blood pressure involves few mechanisms:
 
  • Elevated leptin levels promote sympathetic overactivity resulting in sodium/water retention and vasoconstriction* [1] [2]
  • Increased sodium retention and extracellular fluid volume (therefore increased cardiac output) to service more tissue (despite this there’s an increase in RAAS activation in obesity, probably mainly due to over-activation of the SNS) [1]
  • The physical compression of the kidneys, resulting in lower blood flow to the kidneys, then the kidneys upregulate the RAAS (increase sodium/water retention and total peripheral resistance) to increase blood pressure to maintain GFR [1]
  • In insulin resistant obesity, increased free fatty acids, oxidative stress and inflammation in adipose tissue increases the RAAS and SNS in a positive feedback relationship [2] [3]
 
* People who are overweight/obese are leptin resistant, but the leptin resistance is selective to the arcuate nucleus in the hypothesis, so leptin signalling for body weight regulation is impaired, whereas leptin signalling elsewhere is elevated [2]
 
** Insulin doesn’t seem to raise blood pressure [1].  In addition there’s a lot more evidence for the RAAS increasing IR than IR increasing the RAAS.
 
Cardiovascular Disease
 
Endothelial Dysfunction
 
Nitric oxide is one of the main vasodilators and promotes arterial elasticity [4].  Insufficient nitric oxide impairs endothelial function, which may precede hypertension and lead to kidney failure [5].  Endothelial dysfunction strongly correlates with arterial stiffness, systolic blood pressure and pulse pressure [6].  Superoxide can merge with nitric oxides, which depletes nitric oxide and forms peroxynitrite.  Superoxide is formed mainly by mitochondria, NADPH oxidase and xanthine oxidase (the latter two are activated by the RAAS).  Insulin resistance can also reduce nitric oxide by failing to stimulate Akt production (Akt activates nitric oxide synthase) [7].
 
Atherosclerosis
 
Atherosclerosis is one form of arteriosclerosis, which refers to the stiffening of arteries.  Atherosclerosis is degenerative disease where the artery wall thickens as a result of accumulation of cholesterol, fats, LDLs and immune cells.  Arterial calcification is a common feature of atherosclerosis and it too increases arterial stiffness [8].  As the arteries accumulate more stuff the radius of the artery decreases, which increases total peripheral resistance.  Atherosclerosis in the arteries leading to the kidneys (renal artery stenosis) can cause renovascular hypertension, which is mediated by the RAAS.  Atherosclerosis is associated with increased systolic blood pressure [9].  Hypertension is a risk factor for cardiovascular disease, which may be explained by the effects on blood pressure by atherosclerosis and endothelial dysfunction.  There are many potential factors in atherosclerosis, see Cardiovascular Disease
 
Kidney Function
 
Some of the main functions of the kidneys include the filtering of wastes (urea, ammonia) and the regulation of electrolytes (sodium, potassium, calcium and chlorine).  By regulating electrolytes the kidneys also help to regulate blood volume and blood pressure.  If kidney function is impaired then wastes such as uric acid, creatinine and excess electrolytes aren’t cleared as well and remain elevated in the blood stream, which promotes water retention (through osmosis) and the kidneys will stimulate the RAAS to increase glomerular filtration rate (GFR)*.  Kidney function is a strong influence on blood pressure.
 
“Blood pressure goes with the kidney.  Normotensive recipients of kidneys from hypertensive donors become hypertensive and hypertensive recipients of normotensive kidneys become normotensive” [10]
 
Hypertension is almost certain in end stage renal disease with 80-90 of those needing dialysis being hypertensive [10].  Impaired kidney function reduces blood pressure regulation and makes blood pressure more sensitive to increases in vasoconstriction hormones such as noradrenaline and vasopressin [1].  Poor kidney function (GFR <60) is associated with the metabolic syndrome [11] and diabetic nephropathy is the most common form of renal failure (mediated through hyperglycemia and oxidative stress) [12].
 
* The rate at which the kidneys filter blood.  Healthy kidneys have a GFR of >90 mL/min/1.73m2

Sunday, December 9, 2012

Salt and Blood Pressure

One of the common diet recommendations is that we should reduce our salt (sodium chloride) intake.  The rationale is that lowering salt reduces water retention, which will lower blood volume, therefore lower blood pressure. 

However, blood levels of sodium and blood pressure are some of the most tightly regulated things in the body.  There are many negative feedback mechanisms from the brain, heart, blood vessels and kidneys to maintain blood pressure and sodium levels within a normal range.  For example, on a standard blood test the recommended range for sodium is 135-145 mmol/L, which is only a deviation of 3.6% either way from 140. 

Despite salt being portrayed as the main driver of hypertension, meta-analyses of randomised controlled trials that have reduced salt have only found very mild reductions in blood pressure (see tables below), which suggests dietary sodium doesn’t cause hypertension and is consistent with the negative feedback systems.

[1]
Systolic
Diastolic
Mainly Caucasians – High Blood Pressure
-4.18
-1.98
Mainly Caucasians – Normal Blood Pressure
-1.27
-0.54
African Americans – Normal and High Blood Pressure
-6.44
-1.98

[2]
Systolic
Diastolic
Hypertension
-3.70
-0.90
Normal Blood Pressure
-1.00
-0.10

[3]
Systolic
Diastolic
High Blood Pressure
-3.90
-1.90
Normal Blood Pressure
-1.20
-0.26

[4]
Systolic
Diastolic
Normal and High Blood Pressure
-1.10
-0.60

[5]
Systolic
Diastolic
High Blood Pressure
-4.90
-2.60
Normal Blood Pressure
-1.70
-0.70

[6]
Systolic
Diastolic
Children
-1.17
-1.29
Infants
-2.47

Reducing sodium is not only ineffective for hypertension it also has some undesirable effects.  The sodium reduction in these trials roughly tripled renin and aldosterone levels, increased noradrenaline (norepinephrine) by 30% and adrenaline (epinephrine) by 12% [1] [3].  Renin and aldosterone are part of the renin-angiotensin-aldosterone system (RAAS) and noradrenaline and adrenaline are part of the sympathetic nervous system (fight or flight response).  The RAAS and noradrenaline retain sodium and water.  Reducing sodium can lead to an increase in insulin resistance through noradrenaline [7] and an increase in oxidative stress though the RAAS [8].  It seems that low sodium intakes invoke somewhat of a stress response. 

* Despite being considered ‘heart healthy’, reducing sodium increases total cholesterol by 3.0%, LDL-C by 4.6% and triglycerides by 5.9% [1] 

** A reason why sodium levels are thought to be more important than potassium in blood pressure is because there is much more sodium in the fluid outside of cells (extracellular fluid, ECF) and more potassium in the fluid inside of cells (intracellular fluid, ICF).  Blood is extracellular fluid so changes in sodium would have more effect on blood volume and blood pressure than potassium.  For example on a blood test the recommended range for potassium is 3.7-5.3 mmol/L, whereas sodium is 135-145 mmol/L.

*** Salt-resistance is the norm and means that blood pressure stays relativity constant despite variations in dietary salt, within reason.  Salt-sensitivity is the opposite and refers to blood pressure being sensitive to the amount of salt in the diet.  Salt-sensitivity can occur when the RAAS is unresponsive to changes in salt intake due to the RAAS being too high or being blocked by ACE inhibitors [9].  However, several other systems involved in sodium balance may be impaired in salt-sensitivity [10]

Further Reading
(1) Shaking Up the Salt Myth 

Sunday, December 2, 2012

Blood Pressure

Blood Pressure Basics

When you get your blood pressure measured there are two numbers:

  • Systolic blood pressure (SBP) is the higher number and it measures the pressure in arteries following a contraction of the heart, when the pulse of blood reaches the cuff
  • Diastolic blood pressure (DBP) is the lower number and it measures the pressure in arteries at baseline.  This value reflects how well blood travels from arteries to capillaries and is returned by veins.

From systolic and diastolic you can get two more values:

  • Pulse pressure (PP) is the difference between systolic and diastolic.  It reflects the stroke volume of the heart (the amount of blood pumped each heart beat) and the elasticity of the arteries
          PP = SBP – DBP
  • Mean arterial pressure (MAP) is the average pressure in the arteries, which at 60-70 beats per minute can be estimated by one third systolic and two thirds diastolic or diastolic plus one third pulse pressure, whichever is easiest.  (As heart rate increases mean arterial pressure will increase because there is more pulses from the heart muscle contracting, but the equations assume a normal heart rate)
          MAP = ⅓SBP + ⅔DBP
          MAP = DBP + ⅓PP 

The classification of blood pressure is as follows: 

Systolic (mmHg)
Diastolic (mmHg)
Hypotension
<90
<60
Normal
90-119
60-79
Prehypertension
120-139
80-89
Stage 1 Hypertension
140-159
90-99
Stage 2 Hypertension
≥160
≥100
Isolated Systolic Hypertension
≥140
≤90

* Blood pressure measurements only measure the pressure in arteries.  Blood pressure in veins is much lower (<20 mmHg) 

Factors That Affect Blood Pressure 

Mean arterial pressure is proportional to cardiac output multiplied by the resistance in the arteries (MAP CO x R).  Cardiac output is equal to the stroke volume of each heart beat multiplied by the number of heart beats per minute (CO = SV x HR).  A factor that influences stroke volume is the overall blood volume, which is the idea behind reducing salt.  The resistance in the arteries is proportional to length multiplied by viscosity divided by radius to the power of four* (R Lμ/r4), but viscosity and length don’t really vary much.  The last main factor on blood pressure is arterial elasticity which affects systolic and pulse pressure 

So we have four main factors that could affect blood pressure: cardiac output, blood volume, arterial width/peripheral resistance and arterial stiffness. 

* The body often regulates blood pressure by contracting the smooth muscles of the arteries (vasoconstriction), which decreases the radius, or by relaxing them (vasodilation), which increases the radius.