Arterial Hypertension LECTURE IN INTERNAL MEDICINE FOR V COURSE STUDENTS M. Yabluchansky, L. Bogun, L. Martymianova, O. Bychkova, N. Lysenko, N. Makienko V.N. Karazin National University Medical School’ Internal Medicine Dept. Plan of the Lecture • • • • • • • • • • • • • • Definition Epidemiology Risk factors Etiology Mechanisms Adaptation to arterial hypertension Classification Clinical investigation Diagnosis Treatment Prognosis Prophylaxis Abbreviations Diagnostic guidelines https://edc2.healthtap.com/ht-staging/user_answer/avatars/926769/large/open-uri20130313-20044-zvrt8s.jpeg?1386577375 Definition • Hypertension (HT), also known as high blood (BP) pressure, is a long term medical condition in which the blood pressure in the arteries is persistently elevated • HT defined as values >140 mmHg systolic BP (SBP) and/or >90 mmHg diastolic BP (DBP), based on the evidence from randomized control trials (RCTs) that in patients with these BP values treatment-induced BP reductions are beneficial https://en.wikipedia.org/wiki/Hypertension Epidemiology 1 (Mean Systolic Blood Pressure, Females, Ages 25+) http://image.slidesharecdn.com/bppowerpointwhd2013final-130411023015-phpapp02/95/blood-pressure-world-health-day-2013-13-638.jpg?cb=1365647502 Epidemiology 2 (Mean Systolic Blood Pressure, Males, Ages 25+) http://www.bettycjung.net/BG2013/GlobalBPmen2008.png Epidemiology 3 (Prevalence of High Blood Pressure in USA) cdc.gov Epidemiology 4 Percent prevalence, awareness, treatment, and control of HT in urban and rural communities from high-, middle-, and low-income countries. HT controlled is defined as the proportion of participants with HT with SBP < 140 and DBP < 90 mmHg. HIC, high-income countries; UMIC, upper middle-income countries; LMIC, lower middle-income countries; LIC, low-income countries http://eurheartj.oxfordjournals.org/content/35/6/353 Risk Factors healthy-ojas.com/assets/highbp/highbp-risk-factors.jpg Etiology 1 • HT is classified as either primary (essential) or secondary • About 90–95% of cases are primary, defined as high blood pressure due to nonspecific lifestyle and genetic factors (lifestyle factors that increase the risk include excess salt, excess body weight, smoking, and alcohol) • The remaining 5–10% of cases are categorized as secondary HT, defined as HT due to an identifiable cause, such as chronic kidney disease, narrowing of the kidney arteries, an endocrine disorder, or the use of birth control pills https://en.wikipedia.org/wiki/Hypertension Etiology (?) 2 http://www.dietkundali.com/images/hypertension.jpg Mechanisms 1 (The Control Of Blood Pressure Systems ) • • • • • • • • • Neurogenic Renin-angiotensin Atrial natriuretic peptide Eicosanoids Kallikrein-kinin Endothelial Adrenal steroids Renomedullary vasodepression Sodium and water excretion http://ceaccp.oxfordjournals.org/content/4/3/71.full Mechanisms 2 (Multifactorial And Highly Complex) • • • • • • • • Humoral mediators Vascular reactivity Circulating blood volume Vascular caliber Blood viscosity Cardiac output Blood vessel elasticity Neural stimulation http://emedicine.medscape.com/article/1937383-overview Mechanisms 3 (Key Points) http://image.slidesharecdn.com/hypertension2006path-bw-130410081448-phpapp01/95/hypertension-2013-pathophysiology-26-638.jpg?cb=1366765977 Mechanisms 4 (Short Term Nervous) http://images.slideplayer.com/1/245513/slides/slide_23.jpg Mechanisms 5 (Long Term Humoral) http://image.slidesharecdn.com/hypertension2006path-bw-130410081448-phpapp01/95/hypertension-2013-pathophysiology-14-638.jpg?cb=1366765977 Mechanisms 6 (Combine Peripheral Humoral And Nervous) http://www.poweroverpressure.com/wcm/groups/mdtcom_sg/@mdt/documents/images/pop_angiotensin.gif Mechanisms 7 (Nature of Resistant Hypertension) http://www.hindawi.com/journals/ijhy/2011/196518.fig.001.jpg Adaptation to Arterial Hypertension It lies on the surface (cardiac and vascular remodelling) • Cardiac • structural remodeling of the left ventricle • wall thickening (ventricular hypertrophy) • luminal dilatation • Vascular • structural remodeling of muscular and elastic arteries • wall thickening (hypertrophy) • luminal dilatation In reality changes take place in all systems and structures http://circ.ahajournals.org/content/86/6/1909.full.pdf Classification (European Society of Cardiology) eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf Classification (JNC-7 Blood Pressure Classification) Blood Pressure Classification Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Normal Pre-hypertension Stage 1 hypertension Stage 2 hypertension < 120 120-139 140-159 > 160 < 80 80-89 90-99 > 100 Chobanian AV et al. JAMA 2003;289:2560-72. Classification (Due to Cause) • Essential HT up to 95% • Secondary (inessential) HT – Renovascular ( fibromuscular dysplasia, atheromatous stenosis, diabetes) – Secondary to other renal disorders (cronic renal failure, renal artery stenosis, renal segmental hypoplasia – Secondary to endocrine disorders (pheochromocytoma, hyperaldosteronism (Conn's syndrome), Cushing's syndrome, hyperparathyroidism, acromegaly, hyperthyroidism, hypothyroidism) – Other (hormonal contraceptives, neurologic disorders, obstructive sleep apnea, liquorice, scleroderma, neurofibromatosis, pregnancy, cancers, drugs, etc.) en.wikipedia.org/wiki/Secondary_hypertension Classification (Resistant HT) • Resistant HT is defined as HT that remains above goal blood pressure in spite of using, at once, three antihypertensive medications belonging to different drug classes • Low adherence to treatment is an important cause of resistant HT • Resistant HT may also represent the result of chronic high activity of the autonomic nervous system (neurogenic hypertension) https://en.wikipedia.org/wiki/Hypertension Clinical Investigation (Symptoms) • HT is rarely accompanied by any symptoms, and its identification is usually through screening, or when seeking healthcare for an unrelated problem • Some with high blood pressure report headaches (particularly at the back of the head and in the morning), as well as lightheadedness, vertigo, tinnitus (buzzing or hissing in the ears), altered vision or fainting episodes • These symptoms, however, might be related to associated anxiety rather than the high blood pressure itself en.wikipedia.org/wiki/Hypertension Clinical Investigation (Physical Examination) • Physical examination aims to establish or verify the diagnosis of HT, establish current BP, screen for secondary causes of HT and refine global CV risk estimation • BP should be repeatedly measured to confirm the diagnosis of HT • All patients should undergo auscultation of the carotid arteries, heart and renal arteries • Murmurs should suggest further investigation (carotid ultrasound, echocardiography, renal vascular ultrasound, depending on the location of the murmur) • Height, weight, and waist circumference should be measured with the patient standing, and BMI calculated • Pulse palpation and cardiac auscultation may reveal arrhythmias • Heart rate should be measured while the patient is at rest http://eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf Clinical Investigation (Physical Examination: Signs of Secondary HT ) • • • • • Features of Cushing syndrome Skin stigmata of neurofibromatosis (pheochromocytoma) Palpation of enlarged kidneys (polycystic kidney) Auscultation of abdominal murmurs (renovascular hypertension) Auscultation of precordial or chest murmurs (aortic coarctation; aortic disease; upper extremity artery disease) • Diminished and delayed femoral pulses and reduced femoral blood pressure compared to simultaneous arm BP (aortic coarctation; aortic disease; lower extremity artery disease) • Left–right arm BP difference (aortic coarctation; subclavian artery stenosis) http://eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf Clinical Investigation (Physical Examination: Signs of Organ Damage) • Brain: motor or sensory defects • Retina: fundoscopic abnormalities • Heart: heart rate, 3rd or 4th heart sound, heart murmurs, arrhythmias, location of apical impulse, pulmonary rales, peripheral oedema • Peripheral arteries: absence, reduction, or asymmetry of pulses, cold extremities, ischaemic skin lesions • Carotid arteries: systolic murmurs http://eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf Clinical Investigation (Physical Examination: Evidence of Obesity) • Weight and height • Calculate BMI: body weight/height 2 (kg/m2 ) • Waist circumference measured in the standing position, at a level midway between the lower border of the costal margin (the lowest rib) and uppermost border of the iliac crest http://eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf Clinical Investigation (Hypertensive Crisis) • Severely elevated blood pressure (equal to or greater than a SBP 180 or DBP 110) is referred to as a hypertensive crisis • Hypertensive crisis is categorized as either hypertensive urgency or hypertensive emergency, according to the absence or presence of end organ damage, respectively • In hypertensive urgency oral medications are used to lower the BP gradually over 24 to 48 hours • In hypertensive emergency, the BP must be reduced more rapidly to stop ongoing organ damage, however, there is a lack of randomised controlled trial evidence for this approach https://en.wikipedia.org/wiki/Hypertension Clinical Investigation (Outcomes) • HT is the most important preventable risk factor for premature death worldwide • HT increases the risk of ischemic heart disease, strokes, peripheral vascular disease, and other cardiovascular diseases, including heart failure, aortic aneurysms, diffuse atherosclerosis, chronic kidney disease, and pulmonary embolism • HT is also a risk factor for cognitive impairment and dementia • Other complications include hypertensive retinopathy and hypertensive nephropathy https://en.wikipedia.org/wiki/Hypertension Diagnosis • The evaluation of HT involves accurately measuring the patient’s blood pressure, performing a focused medical history and physical examination, and obtaining results of laboratory and instrumental studies • These steps can help determine the following: – Presence of end-organ disease – Possible causes of HT – Cardiovascular risk factors – Baseline values for judging biochemical effects of therapy emedicine.medscape.com/article/241381-overview Diagnosis (Blood Pressure Measurement) • Office or clinic blood pressure • Out-of-office blood pressure – Ambulatory blood pressure monitoring – Home blood pressure monitoring • White-coat (or isolated office) HT • Masked (or isolated ambulatory) HT - 13% (range 9–16%) - 13% (range 10–17%) http://eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf Diagnosis (Office and Out-of-Office Blood Pressure Criteria) eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf (from True Normotension to Sustained Hypertension) Diagnosis eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf (ABPM Derived Variables) Diagnosis eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf (Total Cardiovascular Risk Stratification) Diagnosis eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf (Risk Factors) Diagnosis eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf (Asymptomatic Organ Damage) Diagnosis eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf (Diabetes Mellitus) Diagnosis eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf (Established Cardiovascular or Renal Disease) Diagnosis eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf (from Predictive Value to Cost–Effectiveness of Some Markers of Organ Damage) Diagnosis eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf (Routine Tests) • Hemoglobin and/or hematocrit • Fasting plasma glucose • Serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol • Fasting serum triglycerides • Serum potassium and sodium • Serum uric acid • Serum creatinine (with estimation of GFR) • Urine analysis: microscopic examination; urinary protein by dipstick test; test for microalbuminuria • 12-lead ECG http://eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf Diagnosis (Additional Tests) • Hemoglobin A1c (if fasting plasma glucose is >5.6 mmol/L (102 mg/dL) or previous diagnosis of diabetes) • Quantitative proteinuria (if dipstick test is positive); urinary potassium and sodium concentration and their ratio • Home and 24-h ambulatory BP monitoring • Echocardiogram • Exercise testing, Holter monitoring in case of arrhythmias • Carotid ultrasound • Peripheral artery/abdominal ultrasound • Pulse wave velocity • Ankle-brachial index • Fundoscopy http://eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf Diagnosis (Extended Evaluation) Diagnosis • Further search for cerebral, cardiac, renal, and vascular damage, mandatory in resistant and complicated hypertension • Search for secondary hypertension when suggested by history, physical examination, or routine and additional tests http://eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf Treatment (Strategies) • Patient education • Lifestyle changes • Pharmacological therapy http://emedicine.medscape.com/article/198475-overview#a3 Treatment (Lifestyle Changes) • Salt restriction • Moderation of alcohol consumption • Other dietary changes (vegetables, low-fat dairy products, dietary and soluble fibers, whole grains and protein from plant sources, reduced in saturated fat and cholesterol) • Weight reduction • Regular physical exercise • Smoking cessation http://emedicine.medscape.com/article/198475-overview#a3 Treatment (Pharmacotherapy) • Diuretics (including thiazides, chlorthalidone and indapamide) • Beta-blockers • Calcium antagonists • Angiotensin-converting enzyme (ACE) inhibitors • Angiotensin receptor blockers • Renin inhibitors • Other antihypertensive agents (alpha-receptor blockers) • Monotherapy and combination therapy http://emedicine.medscape.com/article/198475-overview#a3 (Compelling and Possible Contra-Indications to the Use of Antihypertensive Drugs) Treatment eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf (Drugs to be Preferred in Specific Conditions) Treatment eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf Treatment (Blood Pressure Goals) SBP goal for “most” •Patients at low–moderate CV risk •Patients with diabetes •Consider with previous stroke or TIA •Consider with CHD •Consider with diabetic or non-diabetic CKD <140 mmHg SBP goal for elderly •Ages <80 years •Initial SBP ≥160 mmHg 140-150 mmHg SBP goal for fit elderly Aged <80 years <140 mmHg 140-150 mmHg SBP goal for elderly >80 years with SBP •≥160 mmHg DBP goal for “most” DB goal for patients with diabetes <90 mmHg <85 mmHg eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf Treatment (for People with Diabetes) Recommendations Mandatory: initiate drug treatment in patients with SBP ≥160 mmHg Additonal considerations • Strongly recommended: start drug treatment when SBP ≥140 mmHg SBP goals for patients with diabetes: <140 mmHg DBP goals for patients with diabetes: <85 mmHg All hypertension treatment agents are recommended and may be used in patients with diabetes • RAS blockers may be preferred • Especially in presence of preoteinuria or microalbuminuria Choice of hypertension treatment must take comorbidities into account Coadministration of RAS blockers not recommended SBP, systolic blood pressure; DBP, diastolic blood pressure; RAS, renin –angiotensin system. • Avoid in patients with diabetes eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf Treatment (for People with Nephropathy) Recommendations Additonal considerations Consider lowering SBP to <140 mmHg Consider SBP <130 mmHg with overt proteinuria RAS blockers more effective to reduce albuminuria than other agents Combination therapy usually required to reach BP goals Combination of two RAS blockers Aldosterone antagonist not recommended in CKD SBP, systolic blood pressure; DBP, diastolic blood pressure; RAS, renin –angiotensin system. • Monitor changes in eGFR • Indicated in presence of microalbuminuria or overt proteinuria • Combine RAS blockers with other agents • Not recommended • Especially in combination with a RAS blocker • Risk of excessive reduction in renal function, hyperkalemia eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf Treatment (Comparison of Recent Guideline Statements) JNC 8 ESH/ESC >140/90 Threshold for Drug Rx >140/90 < 60 yr Eldery SBP >160 >150/90 >60 yr Consider SBP 140-150 if <80 yr No Yes >140/90 >140/90 <80 yr >150/90 >80 yr AHA/ACC ASH/ISH B-blocker First line Rx No No Initiate Therapy w/ 2 drugs >160/100 "Markedly elevated BP" >160/100 >160/100 eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf Treatment (Goal Blood Pressure) Group General JNC 8: <60 yr: <140/90 >60 yr: <150/90 < 140/90 BP Goal (mm Hg) DM* < 140/90 CKD** < 140/90 ESH/ESC: < 140/85 < 140/90 Elderly 140-150/90 (<80 yr: SBP<140) (SBP < 130 if proteinuria) ASH/ISH AHA/ACC *ADA: < 140/80 or lower < 140/90 >80 yr: <150/90 < 140/90 < 140/90 < 140/90 < 140/90 < 140/90 (Consider < 130/80 if proteinuria) **KDIGO: <140/90 w/o albuminuria <130/80 if >30 mg/24hr eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf Treatment (Monotherapy vs rug Combination Therapy) eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf Treatment (Possible Combination of Antihypertensive Drugs’ Classes) eurheartj.oxfordjournals.org/content/ehj/34/28/2159.full.pdf Prognosis • Untreated HT is notorious for increasing the risk of mortality and is often described as a silent killer • Mild to moderate HT, if left untreated, may be associated with a risk of atherosclerotic disease in 30% of people and organ damage in 50% of people within 8-10 years after onset • Death from ischemic heart disease or stroke increases progressively as BP increases (for every 20 mm Hg systolic or 10 mm Hg diastolic increase in BP above 115/75 mm Hg, the mortality rate for both ischemic heart disease and stroke doubles) http://emedicine.medscape.com/article/241381-overview#a6 Prophylaxis • Population strategies are required to reduce the consequences of high BP and reduce the need for antihypertensive drug therapy • Lifestyle changes are recommended to lower BP, before starting drug therapy • Effective lifestyle modification may lower blood pressure as much as an individual antihypertensive drug • Combinations of two or more lifestyle modifications can achieve even better results https://en.wikipedia.org/wiki/Hypertension Abbreviations • • • • • • • • • • • • • • • • ABP - ambulatory blood pressure ACE - angiotensin converting enzyme ARB - angiotensin receptor blocker AT - angiotensin BMI - body mass index BB - beta blockers BP - blood pressure CKD - chronic kidney disease CO - carbon oxide CV - cardiovascular DBP - diastolic blood pressure DM - diabetes mellitus ECG - electrocardiography GFR - glomerular filtration rate HDL-C –high density lipoprotein cholesterol HIC -high-income countries • • • • • • • • • • • • • • • HT - arterial hypertension LDL-C – low density lipoprotein cholesterol LIC -low-income countries LMIC - lower middle-income countries LVH - left ventricle hypertrophy LVM - left ventricle mass NO - nitrogen oxide OD - organ demige RAAS – renin angiotensin aldosterone system RF - risk factors RCTs - randomized control trials SBP - systolic blood pressure TC - total cholesterol TG - triglycerides UMIC - upper middle-income countries Diagnostic and treatment guidelines Europe • 2013 ESH/ESC Guidelines for the management of arterial hypertension • Hypertension - National Institute for Health and Care Excellence (nice) guidelines and related materials North America • 2014 Evidence-based guideline for the management of high blood pressure in adults. Report from the panel members appointed to the eighth joint national committee (JNC 8) • British Columbia guidelines on detection, diagnosis and management of hypertension [2015]