Learning Objectives for this filepeople.musc.edu/~decristc/Adv Patho/Unit 5 CV... · 2018-01-23 · LYMPHEDEMA: • Lymphatic channels drain the fluids, lipids & proteins that are

Advanced Pathophysiology Unit 5 CV Page 1 of 55

Filename: advpatho_unit5_4hbp.pdf Source: C. DeCristofaro, MD

Learning Objectives for this file: 1. Review physiology of lymphatics 2. Review control of BP (Sympathetic NS & RAS) 3. Learn about the etiology of hypertension (HTN)(high blood pressure, HBP) as an

imbalance in these systems 4. Learn about the current CPG (Clinical Practice Guideline) for diagnosing HBP in adults 5. Learn about the current CPG for diagnosing HBP in pediatric age groups 6. Learn about the clinical evaluation of HBP, the approach to treatment, and the target (goals) of therapy 7. Be aware of how comorbidities change therapeutic strategies 8. Remember why we “care” about HBP – the resulting CVD morbidities which increase with increasing SBP & DBP 9. Be aware that there are subsets of patients with special needs (e.g., salt responders, & those with resistant HBP)



LYMPHATIC SYSTEM: • special vascular system that returns excess tissue fluid to the heart. • 3 liters/day of fluid that is not reabsorbed into the venous end of the capillary bed by the

usual pressure changes across the capillary. Anatomy:

• lymphatics have closed ends • lymph nodes found along vessels

Function:

• one-way valves • a pumpless system that returns fluid to the circulation via by skeletal muscle &

lymphatic smooth muscle contraction & pulsatile effects of nearby arteries. • Eventually dumps via the thoracic duct into the venous system, & thus back to the heart

for return to circulation.



LYMPHEDEMA: • Lymphatic channels drain the fluids, lipids & proteins that are left in the interstitium after

venous drainage of a tissue bed occurs • Blockage of lymphatic drainage can cause lymphedema • Typically, there is so little protein that the edema is non-pitting Body quadrants of normal superficial lymph drainage Primary lymphedema: improperly formed lymphatics (anatomical variants) • Congenital: 10-25% of all primary lymphedema; may be genetic (Milroy’s diease) • Praecox: most common form (65-80%) of primary lymphedema, occurs after 1 week and

before age 35 yo; usually unilateral • Tarda: (Meige disease), rare, occurs after age 35 yo Secondary lymphedema: THE MORE COMMON PRESENTATION • destruction of normal lymphatics • usually from destruction or removal during surgery of regional lymph nodes • surgery • radiation • infection • tumor invasion and/or compression • burns



Blockage of lymphatic channels causes reverse flow & lymphedema Clinical presentation: • gradual development of swelling • eventually develops a “brawny” nonpitting edema • congested dermal lymphatics cause the peau d’orange • epidermis may develop scaling (keratinization) • Dermatological Complications:

o cracks & furrows allow bacterial entry o lymphorrhea (leakage of lymph onto surface of skin)

Differential diagnosis: • if unilateral and sudden, consider malignancy • other causes of edema (renal insufficiency, heart failure) Treatment; • Medical: compression, weight loss, meticulous attention to skin hygiene • Surgical: excisional techniques of affected area, usually in staged multiple surgeries

(Charles’s procedure is a radical form of this surgery) – only done if medical care fails (see: http://www.lymphedemapeople.com/wiki/doku.php?id=charles_procedure )

http://www.lymphedemapeople.com/wiki/doku.php?id=charles_procedure



LYMPHADENOPATHY: • Benign:

o Can be due to infection of the tissues that these lymph nodes drain o Cat-scratch fever, diphtheria (cervical), EBV mononucleosis(posterior cervical), tonsillitis

(anterior cervical) o Often these lymph nodes are tender (lymphadenitis) o Tender, non-matted nodes suggest infection

• Malignant: o Lymphadenopathy from lymphoma or draining a cancer site o Example is the axillary lymphadenopathy in breast cancer o Non-tender, matted and fixed notes suggest malignancy

Submandibular lymphadenitis in herpetic gingivostomatitis Mononucleosis: Post-auricular Posterior cervical Lymphoma: • Malignancies of the lymphatic system • Include the lymphatic system vessels, the lymph nodes (superficial & deep), and the thymus

& spleen • Lymph is a colorless watery fluid carrying the lymphocytes, thus lymph node malignancy can

travel via the lymphatics • Usually divided into non-Hodgkin’s (NHL, the more common in children) and Hodgkin’s types

NHL in a child



ORTHOSTATIC HYPOTENSION: Definition: • reduction in SBP of at least 20 mm Hg or a reduction in DBP of at least 10 mm Hg during the

first 3 minutes of standing or a head-up tilt on a tilt table o Variant forms:

delayed: occurs after 3 minutes of standing; may be a milder variant or a precursor to full-blown condition

“initial”: drop in BP occurs within 15 seconds of standing Etiology: • sympathetic vasoconstrictor (autonomic) failure • lack of compensatory increase in the heart rate, despite hypotension • milder forms of the condition do have a heart rate increase but it isn’t sufficient to maintain

blood pressure Neurogenic orthostatic hypotension (NOH): • This is a SUBTYPE of orthostatic hypotension that occurs in people with neurologic

disease: o Multiple system atrophy (MSA) o Parkinson’s disease o Pure autonomic failure (PAF) o Diabetic neuropathy o Dopamine beta hydroxylase (DBH) deficiency

Normal physiology of baroreceptor reflex & pathophysiology orthostatic hypotension: • Normal physiology:

o standing results in pooling of 500 to 1000 ml of blood in the lower extremities and splanchnic circulation

o decreased venous return to the heart reduces ventricular filling, resulting in diminished cardiac output and BP

o hemodynamic changes provoke a compensatory reflex response o these are initiated by the baroreceptors in the carotid sinus and aortic arch o result is increased sympathetic outflow and decreased vagal-nerve activity o baroreceptor reflex increases peripheral resistance, venous return to the heart, and

cardiac output, thereby limiting the fall in blood pressure • Pathophysiology:

o failed baroreceptor reflex response o results in orthostatic hypotension and cerebral hypoperfusion

• Epidemiology: o increases in prevalence with age o aging is associated with reduced baroreflex responsiveness, decreased cardiac

compliance, and attenuation of the vestibulosympathetic reflex o NOH occurs in those with neurologic disease

See picture below…



Reminder – the normal baroreceptor reflex; these events are interrupted and blocked in neurogenic hypotension (From: N Engl J Med 7 Feb 2008;358(6):615-24.)

Order of physiologic events: 1. Baroreceptors: are mechanoreceptor sensory terminals of afferent fibers of the

glossopharyngeal and vagus nerves situated in the carotid sinus & aortic notch 2. Decrease in arterial pressure: “unloads” these receptors – this REDUCES normal afferent

impulses through glossopharyngeal and vagus nerves to the nucleus of the tractus solitarius (NTS) in the dorsomedial medulla, resulting in

3. Vagal nerve SA node input reduction: less vagus activity at the sinus node mediated by the neuroanatomical connections of the NTS to the nucleus ambiguus (NA)

4. Increase in sympathetic activity: mediated by the NTS projections to the caudal ventrolateral medulla (CVLM) & from there to the rostral ventrolateral medulla (RVLM) (the RVLM is a “disinhibition” of an inhibitory pathway)

5. Increase in vasopressin (ADH) release: mediated by projections from the A1 noradrenergic cell group in the ventrolateral medulla to the vasopressin-synthesizing neurons of the hypothalamic supraoptic nucleus (SON) & the magnocellular portion of the paraventricular nucleus (PVN).

Picture: Blue denotes sympathetic neurons and green parasympathetic neurons.



CARDIAC PERFORMANCE & BLOOD PRESSURE: Hypereffective heart of athletes: • Training improves compensatory mechanisms • both raised HR & increased SV CO increase • BAD NEWS:

o One of the compensations is LV hypertrophy (LVH) o The LV is stiffer, less compliance – cause a type of heart failure o The LVH requires more Oxygen

Ejection Fraction (EF): • Estimates the health of the heart – it is the ratio of stroke volume (how much blood is ejected

with each systole) to the total filling volume (end-diastolic volume). • Clinical correlates:

o normal heart at rest has EF of 60-65% of its end-diastolic volume o report of an Echocardiogram with Doppler flow study gives the EF, as well as cardiac

catheterization. o can be considered a measure of contractile force (ventricular health)(inotropic

ability). o EF of 50% or less is a failing heart

Diastole = filling Systole = ejection



REMINDER – THE BLOOD PRESSURE (BP): BP = CO x TPR = SV x HR x TPR (Mathematical formula – keep reading...) CO = cardiac output SV = stroke volume HR = heart rate TPR = total peripheral resistance (systemic + venous) • The three factors determining BP are: SV, HR, TPR • In hypertension (high blood pressure), therapeutic targets with lifestyle or drug therapy

will affect those three factors o When thinking about treating hypertension remember what factor is being affected by

the therapeutic intervention • Blood pressure is actually the outward force of the blood against the blood vessel wall

expressed in mm of Hg (the amount of force present will raise a column of mercury to that many mm). This is determined by the force and amount of blood pumped, and the size and flexibility of the arteries.

Think of real-world correlation: • In those with normal circadian cycles, waking in the morning causes increased BP • Sympathetic activation causes:

o Increased chronotropy & inotropy (beta-1 effects) o vasoconstriction (alpha-1 effects)

• RAS activation causes: o Vasoconstriction (Ang-II effects) o Volume increase (ADH & Aldosterone effects)

• All of this increases the MVO2



REMINDER – CARDIAC CONDUCTION: • Remember that abnormal heart rhythms will potentially affect the blood pressure • Affects factors contributing to the BP; 1) filling of the atria and ventricles 2) heart rate

This picture shows the NORMAL Purkinje fiber conduction system that travels from SINUS NODE AV NODE LEFT VENTRICLE

This picture also shows the presence of an ABNORMAL additional (accessory) pathway (sinus node to right ventricle) causing an abnormal EKG tracing (the delta wave in this picture) and predisposing towards arrhythmias.

Good overview of arrhythmias at: http://www.merckmanuals.com/professional/cardiovascular_disorders/arrhythmias_and_conduction_disorders/overview_of_arrhythmias.html?qt=&sc=&alt=

http://www.merckmanuals.com/professional/cardiovascular_disorders/arrhythmias_and_conduction_disorders/overview_of_arrhythmias.html?qt=&sc=&alt

http://www.merckmanuals.com/professional/cardiovascular_disorders/arrhythmias_and_conduction_disorders/overview_of_arrhythmias.html?qt=&sc=&alt



Some electrolyte effects: clinical correlation • Calcium: there is a direct relationship between Ca++ cardiac tone.

o Hypocalcemia (e.g. pancreatitis) causes cardiac flaccidity. o Hypercalcemia (e.g. in cancer, with ectopic production of PTH or tumor lysis

syndrome) causes cardiac spastic contractions due to over-excitation by increased calcium concentrations.

• Potassium: there is an inverse (indirect) relationship between K+ & cardiac tone, HR o Hypokalemia causes increased cardiac tone & contractility, tendency towards certain

arrhythmias). o Hyperkalemia decreases the resting membrane potential (makes it less negative) and

therefore decreases the intensity of the action potential, making the contractions of the heart and conduction pathways weaker & slower (reduced cardiac tone, reduced contractility, tendency towards certain arrhythmias).

Pathway dysfunctions and arrhythmias (dysrhymias): caused by disease or destruction of pacemaker or electrical pathways • Heart block & loss of "atrial kick":

o SA node continues to act, but cannot pass its impulse through the AV node, and one of the bundles in the ventricles takes over as a ventricular pacemaker.

o This results in loss of coordination of the atrial contraction with ventricular filling, and loss of atrial kick (up to 30% of cardiac output).

• Arrhythmias (Dysrhythmias): o Other abnormal rhythms due to abnormal impulse transmission and/or incoordination

of impulse generation o include:

fibrillation or flutter abnormal beats such as escape beats, premature contractions tachy- or brady-arrhythmias.

• Abnormal findings on EKG: o Ectopy: extra beats, premature beats o Tachycardias: rapid rate o Bradycardias: slow rate o Fibrillation: no contraction at all o Ischemia: hypoxemia or outright necrosis (infarct) o Abnormal enlargement: axis deviation, hypertrophy o Conduction blocks : dropped beats o Electrolyte abnormalities : potassium, calcium, magnesium o Accessory pathways of conduction: abnormal tracings and rhythms (e.g. WPW) o Inflammation: myocarditis, pericarditis

• Pathophysiology of arrhythmias: o either disturbances of impulse formation

includes abnormal pacemakers or abnormal pacemaker functioning o and/or disturbances of impulse conduction

depressed conduction reentry/circus conduction due to obstacles to normal conduction with an

abnormal circuit of an impulse entering an area of the heart and exciting it more than once



TYPES OF ATRIAL FIBRILLATION From: January, C.T. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation, Retrieved from http://circ.ahajournals.org/content/early/2014/04/10/CIR.0000000000000041 Paroxysmal AF:

• AF that terminates spontaneously or with intervention within 7 d of onset • Episodes may recur with variable frequency.

Persistent AF:

• Continuous AF that is sustained >7 days Longstanding persistent AF:

• Continuous AF of >12 mo duration Permanent AF:

• Permanent AF is used when there has been a joint decision by the patient and clinician to cease further attempts to restore and/or maintain sinus rhythm.

• Acceptance of AF represents a therapeutic attitude on the part of the patient and clinician rather than an inherent pathophysiological attribute of the AF.

• Acceptance of AF may change as symptoms, the efficacy of therapeutic interventions, and patient and clinician preferences evolve.

Nonvalvular AF:

• AF in the absence of rheumatic mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair.

http://circ.ahajournals.org/content/early/2014/04/10/CIR.0000000000000041



THE RAS & PATHOLOGIC CONDITIONS: Renin-Angiotensin-Aldosterone System (RAS): • Renin is an enzyme released by the JGA (juxta-glomerular apparatus) cells in the kidney

with overall effect of raised BP, improved hydrostatic pressure to the kidney & vital organs, and volume/salt loading.

• GOOD NEWS: o Think of this as an inbuilt way to protect our vital organs from hemorrhage,

dehydration, sepsis, or any other cause of reduced blood flow to vital organs. • Problems with the system:

o chronic activation of this systems leads to pathologic disease conditions o left ventricular remodeling (cardiomegaly) o atherosclerotic heart disease o hypertension.

The Renin-Angiotensin-Aldosterone System Cascade

ACE-Independent PathwayTPA

Cathepsin GTonin

ChymaseCAGE

Angiotensinogen

Angiotensin IBradykinin

Substance P Enkephalins

Other PeptidesAngiotensin II

InactiveFragments

Adapted from Schmieder RE. Am J Hypertens. 2005;18:720−730.

ACE-Dependent Pathway

Tissue: Heart, Brain,Kidney, Arteries

Systemic: Liver

AT1 AT2

ACE

renin

TPA=tissue plasminogen activator; CAGE=chymostatin-sensitive angiotensin II-generating enzyme.

A n g i o t e n s i n R e c e p t o r s



Overall, increased blood volume (salt and water retention), systemic vasoconstriction, cardiac stimulatory effects, and increased blood pressure: • peripheral vasoconstriction • increased afterload (peripheral resistance) • increased preload (venous return) • positive inotropy • positive chronotropy • water and sodium retention by the kidney (increase blood volume) • trophic (stimulates growth) cardiac effects (remodeling of the left ventricle —

cardiomegaly) • fibroblast mitotic (mitogenic) effects (changes at the capillary endothelium results in

accelerated atheroma formation and atherosclerotic cardiovascular disease) • hepatic gluconeogenesis & glycogenolysis (hyperglycemia) • thirst response. General adverse effects of upregulation of Ang-II:





HYPERTENSION (HIGH BLOOD PRESSURE) (HBP): See the CDC Vital Signs website: http://www.cdc.gov/vitalsigns/blood-pressure/index.html

• About 70% of US adults, ages 65 or older, have high blood pressure. • Nearly 50% of adults ages 65 or older with high blood pressure don't have it under

control. • About 5 million adults, ages 65 or older, with Medicare Part D aren't taking their blood

pressure medicine as directed. CDC Fact Sheet: http://www.cdc.gov/vitalsigns/pdf/2016-09-vitalsigns.pdf USPSTF Screening recommendation for hypertension in adults: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/high-

blood-pressure-in-adults-screening CDC Hypertension Prevalence: http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_bloodpressure.htm

http://www.cdc.gov/vitalsigns/blood-pressure/index.html

http://www.cdc.gov/vitalsigns/pdf/2016-09-vitalsigns.pdf

https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/high-blood-pressure-in-adults-screening

https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/high-blood-pressure-in-adults-screening

http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_bloodpressure.htm



PATHOPHYSIOLOGY OF HYPERTENSION: • If long-term elevation of BP occurs, the baroreceptor feedback mechanism will "reset" and

adapt to the prevailing BP. • This means that the body "gets used to" an abnormal BP level. • The reset involves renin levels, sympathetic tone, and failure of baroreceptors to stimulate

parasympathetic outflow Etiology of primary (essential) HBP: • Rise in TPR from vasoconstriction due to Ang-II & catecholamines • Rise in vascular volume from volume loading with Na & water (due to aldosterone & ADH) • Thus, the etiology is from the RAS, or sympathetic NS, or both:

o RAS system: (endocrine) this BOTH alters blood volume AND causes vasoconstriction.

o Sympathetic NS: (nervous system) catecholamine positive chronotropy & inotropy, vasoconstriction

• However: High resting pulse rate does predict future HBP, but most persons with HBP do NOT have increased circulating catecholamines

• Genetic contribution: o genetics contribute to hypertension development o also affect response to BP medications and cardiovascular disease outcomes o genes include ACE polymorphisms, beta-receptor SNPs, bradykinin receptor SNPs,

alpha-receptor SNPs o 2011 Hypertension journal article on heart rate & HBP:

http://hyper.ahajournals.org/content/58/5/745.short

http://hyper.ahajournals.org/content/58/5/745.short



Hypertension Is thus also an Endocrine disorder since the Renin Angiotensin System (RAS) is activated

Hypertension is a Neurologic disorder Sympathetic outflow affects cardiac and vascular systems, and activates the RAS



Etiology of Secondary HBP: • develops from secondary causes that may be correctable • these are called identifiable causes of high blood pressure • Some examples are:

1) Sleep apnea 2) Drug-induced (e.g. NSAID, steroid therapy, cocaine) 3) Chronic kidney disease (CKD) 4) Primary aldosteronism (tumor) 5) Renovascular disease (renal artery stenosis) 6) Cushing’s syndrome (steroid excess) 7) Coarctation of the aorta 8) Thyroid disease 9) Parathyroid disease

Final results of longstanding untreated hypertension: • Often called the "silent disease” or “silent killer" since patient typically has no symptoms • TOD – target organ damage:

o End-organ damage is continuing without the patient’s knowledge o This is why screening is important due the lack of symptoms

• CCD – clinical cardiovascular disease: o These conditions result from arteriosclerosis (age related changes) o AND from the hormonal and neurologic changes that underlie the development of

hypertension • The longer HBP exists, the more progressive are the damages to the vessels and organs CCD (clinical cardiovascular disease): ALL these conditions cause morbidity & mortality

• Heart diseases (LVH, angina or prior MI, prior coronary revascularization, HF) • stroke or TIA • peripheral arterial disease.

Million Hearts Initiative and ABCS: • Million Hearts® is a national initiative of the Department of Health and Human • Promotes the "ABCS" of clinical prevention:

o appropriate aspirin therapy o blood pressure control o cholesterol management o smoking cessation

• As well as supporting healthier lifestyles and communities • See: http://millionhearts.hhs.gov/index.html

http://millionhearts.hhs.gov/index.html



HOW TO TAKE THE CLINICAL BLOOD PRESSURE: From: https://professional.heart.org/professional/ScienceNews/UCM_496965_2017-Hypertension-Clinical-Guidelines.jsp

• For home measurements, do these in the morning before taking any medications and again in the evening before dinner

https://professional.heart.org/professional/ScienceNews/UCM_496965_2017-Hypertension-Clinical-Guidelines.jsp




OUR CUTOFF TO MAKE A DX OF HBP? Evidence Base WHAT IS HAPPENING IN THE ARTERIES WITH HBP?

The vertical axis on the graph is “RELATIVE RISK” Relative risk (RR): • < 1 means risk is

less than general population

• 0 means risk is the same as the general population

• > 1 means risk is greater than general population

The BP value that is associated with an RR of > 1 is when the BP is 130/80 or greater. RR information determines optimal BP values.

O2 Endothelial Cells and H2O2 Vascular Smooth Muscle

Oxidative Stress: Endothelial Oxidative Stress: Endothelial Dysfunction and CAD/Renal Risk FactorsDysfunction and CAD/Renal Risk Factors

Capillary Endothelial Dysfunction

Apoptosis

VasoconstrictionLeukocyteadhesion

Lipiddeposition

ThrombosisVSMCgrowth

Hypertension SmokingDiabetes LDL-C



TOD (target organ damage): retinal, cardiac, brain, kidney, vascular (see examples below) • retinal (hypertensive retinopathy) • cardiac

o hypertensive cardiomyopathy o LVH o HF o ASHD & angina

• cerebrovascular disease (stroke/CVA) from arteriolar sclerosis – HBP is a greater risk factor for stroke than for ASHD

• renal failure (hypertensive nephropathy and nephrosclerosis) • vascular (aortic aneurysm & dissection). • Smoking is also an independent risk factor for ASHD & Stroke



Pathology of TOD: Arterial oxidative stress Histologic pathologic changes: • VASCULAR:

o arteriolar sclerosis (“hyalinized arterioles”) o narrowing of the small arteries through “hyaline” basement membrane change

Narrowing of the artery due to hyaline arteriosclerosis. This narrows the vessel and impairs vasoconstriction and vasodilatation for normal vascular responses. Note the concentric thickening. This becomes progressively worse. Final organ dysfunctions include nephrosclerosis, retinopathy,

• TISSUE:

o interstitial fibrosis o globally sclerotic glomeruli



Example of TOD – nephropathy: Example of TOD – retinopathy:

Correlation Between SBP andRenal Function

GFRdecline

(mL/min/y)

0

-2

-4

-6

-8

-10

-12

-14

SBP (mm Hg)130 134 138 146142 150 154 170 180

r=0.69; P<0.05

UntreatedHTN

GFR, glomerular filtration rate; HTN, hypertension.Adapted from Bakris GL et al. Am J Kidney Dis. 2000;36:646-661.



Example of TOD – hypertensive dilated cardiomyopathy: Example of TOD – hypertension and heart failure:



What about SALT and hypertension? • 40% of hypertensives will have their BP increase with dietary salt (NaCl) – called “salt

responders” • these salt responders are also more likely to suffer from CVA (stroke) • Many are African-American (up to 40% of these patients are salt responders)



DASH Diet Components• For a 2,100 calorie daily diet• Increased potassium from fruits, vegetables,

nuts and low-fat dairy

DASH Diet Effect on BP

Sacks FM, Campos H. Dietary Therapy in Hypertension. N Engl J Med3 June 2010; 362(22):2101-12.



AHA 2006 HEART-HEALTHY PREVENTION DIET

http://circ.ahajournals.org/cgi/content/short/CIRCULATIONAHA.106.176158v2

High Sodium, High Calorie Diet

acks FM, Campos H. Dietary Therapy in Hypertension. N Engl J Med June 2010; 362(22):2101-12.

Low Sodium, Low Calorie Diet

Sacks FM, Campos H. Dietary Therapy in Hypertension. N Engl J Med June 2010; 362(22):2101-12.



Overall lifestyle approach: (from AHA/ACC 2017 guidelines) Some other terms you might hear: WHITE-COAT HYPERTENSION (WCH): • “white-coat” hypertension means that the BP is higher when being measured by a clinician • it has been shown that this is related to CV risk (atherosclerosis) • this has been shown to be related to obesity and metabolic syndrome (MetSyn) • at least one study has shown a blunting of WCH effect by using metformin, a diabetes drug

that reduces appetite and is sometimes used to manage MetSyn • WCH needs to be treated and may in fact be a predictor of more severe CV risk “LABILE” HYPERTENSION: • persons with blood pressure elevations that are only intermittent also need treatment • labile hypertension has been shown to be associated with CV risk • investigate causes?

o salt responder – more at risk of stroke (limit salt in diet consistently) o illicit drugs (e.g. cocaine) o use of OTC drugs (e.g. all NSAIDs and dose-related to acetaminophen)

NSAIDs raise BP and cause edema Acetaminophen raises BP in a dose-related way:

• Men if used 6-7 days/week (risk higher in heavier men)** • Women if used > 15 days/month, or doses >500 mg/day*



Think in terms of what can be modified and what cannot:



DIAGNOSIS OF HYPERTENSION (HTN) – HIGH BLOOD PRESSURE (HBP) IN PEDIATRICS: Current American Academy of Pediatrics (AAP) CPG (2017): http://pediatrics.aappublications.org/content/early/2017/08/21/peds.2017-1904 NIH integrated guidelines for cardiovascular health in pediatrics: https://www.nhlbi.nih.gov/node/80139 Definition of HBP in adults & children: • BP values defined differently for adults & children

o For children, age & sex charts must be used (found in report above & other manuals) • For adults, there are values for normal, prehypertension, Stage 1 & Stage 2 CHILDREN & ADOLESCENTS: All of the following information for pediatrics is from the 2017 AAP CPG

• The term “prehypertension” has been replaced with “elevated hypertension” • Note that the definition of HTN is based on norms by age & sex

http://pediatrics.aappublications.org/content/early/2017/08/21/peds.2017-1904

https://www.nhlbi.nih.gov/node/80139



Although normative tables are provided in the CPG, a simplified table to identify those needing additional evaluation is provided: t is important to use proper BP cuff size:



The CPG provides “key action statements” to guide management: (See also next page)





An algorithm is provided for screening process:



The evaluation (workup) for pediatrics is comprehensive:



Findings that may suggest secondary cause of hypertension in children: The guideline also gives details on clinical follow-up and pharmacological management.



DIAGNOSIS OF HYPERTENSION (HTN) – HIGH BLOOD PRESSURE (HBP) IN NONPREGNANT ADULTS: Note all AHA statements and guidelines can be accessed at: http://my.americanheart.org/professional/StatementsGuidelines/Statements-Guidelines_UCM_316885_SubHomePage.jsp Current AHA/ACC hypertension guideline (2017): https://professional.heart.org/professional/ScienceNews/UCM_496965_2017-Hypertension-Clinical-Guidelines.jsp Prevalence:

• increases with age until age 80 • more African-American (blacks) than whites • 90% have essential (primary) HTN

Typical abbreviations used in the guidelines: • SBP = systolic blood pressure • DBP = diastolic blood pressure • HTN = hypertension • HBP = high blood pressure

Guidelines history:

• The Joint National Commission (JNC) of the National Institutes of Health (NIH), National Heart, Lung and Blood Institute (NHLBI) wrote the guidelines for many years

• In 2013 the AHA/ACC began updating the guidelines as well as other professional societies

• Which guideline to follow? o We had an update called JNC-8 in 2014 which as different from the existing

AHA/ACC guidelines • Evolution of terms and stages of HTN:

o Originally, in the first JNC, the focus was on DBP o Later JNC and current guidelines focused more on SBP o There used to be a term “isolated systolic hypertension (ISH) of the elderly” o There used to be terms “high normal BP” and “prehypertension”

• Guidelines in use: o AHA/ACC (2017) (NOT endorsed by the AAFP) o JNC-8 (2014) o AAFP/ACP (2017) o Specialty guidelines (e.g., diabetes association)

See more on the history below

http://my.americanheart.org/professional/StatementsGuidelines/Statements-Guidelines_UCM_316885_SubHomePage.jsp

http://my.americanheart.org/professional/StatementsGuidelines/Statements-Guidelines_UCM_316885_SubHomePage.jsp





Development of JNC over the years – why has it “gone away”? • History of NIH & NHLBI:

– National Institutes of Health (1940) – per President Roosevelt, “we cannot be a strong nation unless we are a healthy nation”

– National Heart, Lung, and Blood Institute’s (NHLBI) core mission is the generation and dissemination of knowledge and science with the goal of securing a healthy nation.

• History of JNC: – July 26, 1972: Elliot Richardson (Secretary of the US Department of Health,

Education, and Welfare) established “National Hypertension Program.” – 1977: NHLBI issued the first of its clinical practice guidelines (CPGs) – Joint National

Commission (two agency committees) • Institute of Medicine Report (2011):

– 2008: U.S. Congress (via Medicare Improvements for Patients and Providers Act) asks IOM to study the best methods for developing clinical practice guidelines

– 2011: IOM report sets standards for development of CPGs • NHLBI Advisory Council (NHLBAC) evaluates NIH/NHLBI health education portfolio and

appoints special working groups of the NHLBAC to provide guidance on options • Plan to refocus health education agenda on core mission of knowledge generation and

synthesis by supporting and producing rigorous systematic reviews which can be used by other collaborating organizations to generate CPGs

• Change in process announced June 19, 2013 • NHLBI asked the AHA & ACC to jointly write upcoming integrated guidelines for:

– Hyperlipidemia – Hypertension – Cardiovascular Risk Assessment – Cardiovascular Lifestyle Interventions – Obesity

“….we plan to refocus our health education agenda on our core mission of knowledge generation and synthesis by supporting and producing rigorous systematic reviews that can then be used by other collaborating organizations to generate guideline products that serve the public interest. The NHLBI has decided that the five integrated cardiovascular guideline products will be published as evidentiary reviews, and that the Institute will subsequently collaborate with other organizations to prepare and issue the related clinical practice guidelines.” Gibbons GH, et al. Refocusing the Agenda on Cardiovascular Guidelines: An Announcement from the National Heart, Lung, and Blood Institute. Circulation (June 19, 2013) At: http://circ.ahajournals.org/content/early/2013/06/18/CIRCULATIONAHA.113.004587.citation National Academy of Sciences. Institute of Medicine report on Finding What Works in Health Care: Standards for Systematic Reviews : http://www.iom.edu/Reports/2011/Finding-What-Works-in-Health-Care-Standards-for-Systematic-Reviews.aspx

http://circ.ahajournals.org/content/early/2013/06/18/CIRCULATIONAHA.113.004587.citation

http://www.iom.edu/Reports/2011/Finding-What-Works-in-Health-Care-Standards-for-Systematic-Reviews.aspx

http://www.iom.edu/Reports/2011/Finding-What-Works-in-Health-Care-Standards-for-Systematic-Reviews.aspx



OLDER (JNC-7 and JNC-8) Diagnostic classifications in ADULTS – ALSO USED by the AAFP/ACIP guidelines: NEWER AHA/ACC 2017 diagnostic classifications in ADULTS (summary):



EVALUATION PRIOR TO TREATMENT: HYPERTENSIVE URGENCY & HYPERTENSIVE EMERGENCY:



FIRST – JNC-8 GUIDELINES (2014): • Written by the authors originally invited to write JNC-8 • However, not endorsed by the AHA, ACC, NIH or CDC James PA, Oparil S, Carter BL, et al. (2014) 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), JAMA. doi:10.1001/jama.2013.284427. Download At: http://jama.jamanetwork.com/article.aspx?articleid=1791497 JNC-8 for the general adult population 60+ years old: JNC-8 for the general adult population <60 years old:

http://jama.jamanetwork.com/article.aspx?articleid=1791497



JNC-8 – those with CKD: Estimated GFR or measured GFR less than 60 mL/min/1.73 m2 and in people of any age with albuminuria defined as greater than 30 mg of albumin/g of creatinine at any level of GFR JNC-8 those with DM: JNC-8 – Black vs. Non-black:



JNC-8 management to achieve goals: SEE BELOW FOR OVERALL ALGORITHM



JNC-8 Overall Algorithm:



ANOTHER GUIDELINE RELEASED IN 2017 – endorsed by AAFP and ACP: Qasseem, A., et al. (2017) Pharmacologic treatment of hypertension in adults aged 60 years or

older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Annals of Internal Medicine, Retrieved from http://annals.org/aim/article/2598413/pharmacologic-treatment-hypertension-adults-aged-60-years-older-higher-versus

Recommendation 1: ACP and AAFP recommend that clinicians initiate treatment in adults aged 60 years or older with systolic blood pressure persistently at or above 150 mm Hg to achieve a target systolic blood pressure of less than 150 mm Hg to reduce the risk for mortality, stroke, and cardiac events. (Grade: strong recommendation, high-quality evidence). ACP and AAFP recommend that clinicians select the treatment goals for adults aged 60 years or older based on a periodic discussion of the benefits and harms of specific blood pressure targets with the patient. Recommendation 2: ACP and AAFP recommend that clinicians consider initiating or intensifying pharmacologic treatment in adults aged 60 years or older with a history of stroke or transient ischemic attack to achieve a target systolic blood pressure of less than 140 mm Hg to reduce the risk for recurrent stroke. (Grade: weak recommendation, moderate-quality evidence). ACP and AAFP recommend that clinicians select the treatment goals for adults aged 60 years or older based on a periodic discussion of the benefits and harms of specific blood pressure targets with the patient. Recommendation 3: ACP and AAFP recommend that clinicians consider initiating or intensifying pharmacologic treatment in some adults aged 60 years or older at high cardiovascular risk, based on individualized assessment, to achieve a target systolic blood pressure of less than 140 mm Hg to reduce the risk for stroke or cardiac events. (Grade: weak recommendation, low-quality evidence). ACP and AAFP recommend that clinicians select the treatment goals for adults aged 60 years or older based on a periodic discussion of the benefits and harms of specific blood pressure targets with the patient.

http://annals.org/aim/article/2598413/pharmacologic-treatment-hypertension-adults-aged-60-years-older-higher-versus

http://annals.org/aim/article/2598413/pharmacologic-treatment-hypertension-adults-aged-60-years-older-higher-versus



2017 AHA/ACC GUIDELINE: Risk factors for CVD in those with HTN: Categories of HTN:



Algorithm: (the “classes” on this graphic relate to the strength of evidence)



Screening for secondary hypertension:



When do you get DRUGS??? What are the target BP goals??? REMEMBER – for each patient with hypertension, you MUST:

• evaluate for clinical CVD (h/o MI, stroke, PAD) • OR • obtain the ASCVD risk percentage via:

http://static.heart.org/riskcalc/app/index.html#!/baseline-risk?utm_campaign=sciencenews17-18&utm_source=science-news&utm_medium=phd-link&utm_content=phd11-13-17_htn-gl






Lifestyle interventions & expected benefit:



Follow-up after initial BP evaluation:



Selected specific recommendations for those with comorbidities: Stable ischemic heart disease (SIHD):

• BP target less than 130/80 • Drugs recommended include guideline-directed medical therapy (GDMT) with beta-

blockers, ACEI/ARB, and additional drugs as needed (diuretics, DHB CCB, aldosterone antagonists)

• If also have angina, add CCB Heart failure:

• BP target less than 130/80 • GDMT therapeutics if heart failure with preserved ejection fraction (diuretics, ACEI/ARB) • Avoid non-DHP CCBs

Chronic kidney disease (CKD): BP target less than 130/80 ACEI to slow progression (ARB if ACEI not tolerated) Additional information in the guideline for acute intracerebral hemorrhage, acute ischemic stroke, secondary stroke prevention, peripheral artery disease, DM, atrial fibrillation, valvular heart disease, aortic disease, and those undergoing surgical procedures. NOTE that the target BP for DM is listed as <130/80, which is different from that recommended in the 2018 Diabetes Association guidelines. Selected specific recommendations for patient subpopulations: African-American/Black:

• If no HF or CKD, use diuretic and CCB • Recognize that 2 or more drugs will probably be necessary to achieve target BP

Women who may become pregnant:

• Avoid ACEI, ARB, DRI • Transition to methyldopa, nifedipine or labetolol during pregnancy

Older adults:

• May treat to a different intensity of BP management as needed



Resistant Hypertension:



THERE ARE ALSO HYPERTENSION GUIDELINES FOR DIABETES from the ADA: Hypertension in the diabetic – updated annually by the American Diabetes Association (2018): http://care.diabetesjournals.org/content/41/Supplement_1/S86 ADA guidelines and hypertension in DM 2018 Specifics of lifestyle and pharmacologic management are also given in the guideline

http://care.diabetesjournals.org/content/41/Supplement_1/S86

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