Essential Hypertension 14/01/2019

Hypertension Hypertension is not a disease It is an arbitrarily defined disorder to which both environmental and genetic factors contribute Major risk factor for: cerebrovascular disease myocardial infarction heart failure peripheral vascular disease renal failure 14/01/2019

This left ventricle is very thickened (slightly over 2 cm in thickness), but the rest of the heart is not greatly enlarged. This is typical for hypertensive heart disease. The hypertension creates a greater pressure load on the heart to induce the hypertrophy. 14/01/2019

The left ventricle is markedly thickened in this patient with severe hypertension that was untreated for many years. The myocardial fibers have undergone hypertrophy. 14/01/2019

The definition of hypertension has been arbitrarily set as: Blood pressure is a continuous variable which fluctuates widely during the day physical stress mental stress The definition of hypertension has been arbitrarily set as: That blood pressure above which the benefits of treatment outweigh the risks in term of morbidity and mortality 14/01/2019

Blood Pressure Exhibits a normal distribution within the population Increasing blood pressure is associated with a progressive increase in the risk of stroke and cardiovascular disease Risk however rises exponentially and not linearly with pressure 14/01/2019

At what blood pressure is a patient hypertensive? BHS 140/90 JNC-VI 140/90 Opt <120/<80 WHO-ISH 140/90 The current recommendation in the UK is 140/90 However risk is important and in diabetes 130/80 14/01/2019

In 95% of cases no cause can be found In 5-10% a cause can be found Chronic renal disease Renal artery stenosis Endocrine disease, Cushings, Conn’s Syndrome, Phaeochromocytoma, GRA 14/01/2019

Risks of Hypertension The risk of hypertension is considerable The 4th most common cause of death world-wide Directly and indirectly responsible for >20% of all deaths The risks of hypertension have been most thoroughly determined by the Framingham Study - a longitudinal study performed in the USA 14/01/2019

Framingham Study This study clearly demonstrated that the relative risk to a patient with a DBP of 99 mmHg compared to a DBP of 84 mm Hg for Stroke increases 4 fold MI increases 2 times The same was also found to be true for systolic blood pressure These pressure are common 14/01/2019

Despite the clear relationship between blood pressure and morbidity the risk from hypertension also depends on and increases exponentially with other factors Cigarette smoking Adds 20/10 mmHg Diabetes mellitus 5-30 X increase MI Renal disease Male 2X risk Hyperlipidaemia Previous MI or stroke Left ventricular hypertrophy 2X risk 14/01/2019

Control of blood pressure Blood pressure is controlled by an integrated system Prime contributors to blood pressure are: Cardiac output Stroke volume Heart rate Peripheral vascular resistance Each of these factors can be manipulated by drug therapy 14/01/2019

Sympathetic Nervous System Sympathetic system activation produces vasoconstriction reflex tachycardia increased cardiac output In this way blood pressure is increased The actions of the sympathetic system are rapid and account for second to second blood pressure control 14/01/2019

The renin-angiotensin-aldosterone system The RAAS is pivotal in long-term BP control The RAAS is responsible for: maintenance of sodium balance control of blood volume control of blood pressure 14/01/2019

The RAAS is stimulated by: fall in BP fall in circulating volume sodium depletion Any of the above stimulate renin release from the juxtaglomerular apparatus Renin converts angiotensinogen to angiotensin I Angiotensin I is converted to angiotensin II by angiotensin converting enzyme (ACE) 14/01/2019

Angiotensin II is a potent vasoconstrictor anti-natriuretic peptide stimulator of aldosterone release from the adrenal glands Aldosterone is also a potent antinatriuretic and antidiuretic peptide Angiotensin II is also a potent hypertrophic agent which stimulates myocyte and smooth muscle hypertrophy in the arterioles 14/01/2019

Myocyte and smooth muscle hypertrophy: are both poor prognostic indicators in patients with hypertension partially explain why hypertension and the risks of hypertension persist in some patients despite treatment Both the sympathetic and RAAS are key targets in the treatment of hypertension 14/01/2019

Aetiology of essential hypertension The aetiology of hypertension is Polygenic Major genes Poly genes Polyfactorial Environment Individual and Shared 14/01/2019

A sodium homeostatic effect Likely causes: Increased reactivity of resistance vessels and resultant increase in peripheral resistance as a result of an hereditary defect of the smooth muscle lining arterioles A sodium homeostatic effect In essential hypertension the kidneys are unable to excrete appropriate amounts of sodium for any given BP. As a result sodium and fluid are retained and the BP increases 14/01/2019

Other factors Age Genetics and family history Environment Weight Alcohol intake Race 14/01/2019

AGE BP tends to rise with age, possibly as a result of decreased arterial compliance. Hypertension in the elderly should be treated as aggressively as in the young. They have more to lose Studies such as EWPHE, Primary Care Study,MRC Hypertension in the Older Adult, SHEP, SYSTEUR and STOP-1 and 2 have proven that treating both diastolic and systolic hypertension in the elderly significantly reduces stoke and MI. 14/01/2019

GENETICS A history of hypertension tends to run in families The closest correlation exists between sibs rather than parent and child It is also possible that environmental factors common to members of the family also have a role in the development of hypertension 14/01/2019

Environment Mental and physical stress both increase blood pressure However removing stress does nor necessarily return blood pressure to normal values True stress responders who have very high BP when they attend their doctor but low normal pressures otherwise tend to be highly resistant to treatment 14/01/2019

Sodium Intake The SALT study and more recently the DASH study have confirmed a strong relationship between hypertension, stroke and salt intake Reducing salt intake in hypertensive individuals does lower blood pressure However reducing salt intake in normotensives appears to have no effect Reducing salt intake to <1.5gm/day or better <0.5gm/day does lower BP However there are real difficulties in achieving this level of salt restriction (fast food) 14/01/2019

ALCOHOL The most common cause oh hypertension in the young Scot Affects 1% of the population Small amounts of alcohol tend to decrease BP Large amounts of alcohol tend to increase BP If alcohol consumption is reduced BP will fall over several days to weeks. Average fall is small 5/3 mmHg 14/01/2019

Weight Obese patients have a higher BP Up to 30% of hypertension is attributable in part or wholly to obesity If a patient loses weight BP will fall In untreated patients a weight loss of 9Kg has been reported to produce a fall in BP of 19/18 mmHg In treated patients a fall in BP of 30/21 mmHg has been reported Weight reduction is the most important non-pharmacological measure available 14/01/2019

Birth Weight Birth weight is also associated with the development of hypertension in later life. The lower the birth weight the higher the likelihood of developing hypertension and heart disease Clearly in-utero factors affect health at a later stage. 14/01/2019

Race Caucasians have a lower BP than black populations living in the same environment Black populations living in rural Africa have a lower BP than those living in towns Reasons are not clear Possibly black populations are more susceptible to stress when living in towns Respond in different ways to changes in diet Black populations are genetically selected to be salt retainers and so are more sensitive to an increase in dietary salt intake 14/01/2019

Secondary Hypertension 5-10% of all hypertension has an identifiable cause Removal of the cause does not guarantee that the hypertension or risk will return to normal Sustained hypertension produces end-organ damage to blood vessels, heart and kidney This type of damage tends to increase BP further and so a vicious self-propagating cycle is established 14/01/2019

Causes for Secondary Hypertension Renal disease 20% of resistant hypertensive patients chronic pyelonephritis renal artery stenosis polycystic kidneys Drug Induced NSAIDs Oral contraceptive Corticosteroids 14/01/2019

Pregnancy Endocrine Vascular Sleep Apnoea pre-eclampsia Conn’s Syndrome Cushings disease Phaeochromocytoma Hypo and hyperthyroidism Acromegaly Vascular Coarctation of the aorta Sleep Apnoea 14/01/2019

The risks of hypertension The risks of hypertension are well recognised Cerebrovascular disease Thromboembolic Intra cranial bleed TIA Cardiovascular disease Myocardial infarction Heart failure Coronary artery disease 14/01/2019

The risks of hypertension Peripheral vascular disease Renal failure 14/01/2019

The risks of hypertension A sustained increase in BP increases the load on the heart and blood vessels This has two effects Myocardial hypertrophy Smooth muscle hypertrophy in the resistance vessels Hypertrophy of this type increases the strength of the heart and vasculature However it also reduces compliance 14/01/2019

The effects of reduced compliance are: A reduction in the ability of the heart to to respond to increased or variable loads a decrease in the ability of the resistance vessels to relax For the same level of BP and irrespective of age the presence of left ventricular hypertrophy increases 5 year mortality by 33% in men 21% in women 14/01/2019

Atheromatous disease The Heart Sustained hypertension is associated with accelerated atheromatous disease of the blood vessels Peripheral vascular disease Coronary artery disease Cerebrovascular disease Renal artery disease The Heart MI Heart failure Angina 14/01/2019

Detection and Diagnosis Initial assessment History Office blood pressure ABPM Abdominal ultrasound scan Inpatient assessment Assess risk Smoking Diabetes Previous pathology 14/01/2019

The Aetiology of Hypertension 14/01/2019 Hypertension Medication for High Blood Pressure Diuretics Rid the body of excess fluids and salt Beta-blockers Reduce the heart rate and the work of the heart Calcium antagonists Reduce heart rate and relax blood vessels 14/01/2019 Clinical Pharmacology Phase II

The Aetiology of Hypertension 14/01/2019 Hypertension Medication for High Blood Pressure Angiotensin II receptor blockers(ACE) Interfere with the bodies production of angiotensin, a chemical that causes the arteries to constrict (narrow) Vasodialators Cause the muscle in the wall of the blood vessels to relax, allowing the vessel to dialate (widen) 14/01/2019 Clinical Pharmacology Phase II

The Aetiology of Hypertension 14/01/2019 Hypertension Medication for High Blood Pressure Sympathetic nerve inhibitors Sympathetic nerves go from the brain to all parts of the body, including the arteries Cause arteries to constrict raising blood pressure These drugs reduce blood pressure by inhibiting these nerves from constricting blood vessels 14/01/2019 Clinical Pharmacology Phase II

The Aetiology of Hypertension 14/01/2019 Hypertension Home Blood Pressure Monitoring Mercury sphygmomanometer Standard for BP monitoring No calibration May be bulky Need a second person to use machine May be difficult for hearing impaired or patients with arthritis 14/01/2019 Clinical Pharmacology Phase II

The Aetiology of Hypertension 14/01/2019 Hypertension Home Blood Pressure Monitoring Aneroid equipment Inexpensive, lightweight and portable Two person operation/need stethoscope Delicate mechanism, easily damaged Needs calibration with mercury sphygmomanometer 14/01/2019 Clinical Pharmacology Phase II

The Aetiology of Hypertension 14/01/2019 Hypertension Home Blood Pressure Monitoring Automatic equipment Contained in one unit Portable with easy-to-read digital display Expensive, fragile Must be calibrated Requires careful cuff placement 14/01/2019 Clinical Pharmacology Phase II

TARGET <140 mm Hg systolic and < 90 mmHg diastolic Treatment of Adults with Systolic-Diastolic Hypertension without Other Compelling Indications TARGET <140 mm Hg systolic and < 90 mmHg diastolic INITIAL TREATMENT AND MONOTHERAPY Lifestyle modification therapy Thiazide ACE-I ARB Long-acting CCB Beta- blocker* * Not indicated as first line therapy over 60 14/01/2019

Summary: Treatment of Hypertension without Other Compelling Indications TARGET <140 mm Hg systolic and < 90 mmHg diastolic Lifestyle modification therapy Thiazide diuretic ACE-I ARB Long-acting CCB Beta- blocker* CONSIDER Nonadherence? Secondary HTN? Interfering drugs or lifestyle? White coat effect? Dual Combination Triple or Quadruple Therapy * Not indicated as first line therapy over 60 14/01/2019

Thank you for attention! 14/01/2019