Hypertension
Liddle's Syndrome Therapy
*Amiloride* (K-sparing diuretic that directly closes the Na channels) - (Triamterene works also, but we tend to avoid triamterene because it may result in kidney stones in some patients) ("*Ami-liddle-ride*: Amilodiride to treat Liddle Syndrome")
Four year progression of Hypertension: Framingham Heart Study
*Without lifestyle modification in pre-hypertensive patients, HTN develops* - JNC 7 changed to identify this population
Risk Factors for Development of HTN
- *Age*: prevalence of HTN increases with age. - *Family history*: twice as common if 1 or 2 parents have HTN - *Race*: higher likelihood of HTN in African Americans compared to Caucasians - *Gender*: men have an increased risk (women catch up in the postmenopausal years) - *Weigh*t: people with higher than optimal weight (BMI > 27 kg/m) have increase risk of HTN - *Psychosocial stress*: chronic stress is associated with HTN - *Diet*: high sodium, low potassium increase risk of HTN - *Behavioral*: heavy alcohol intake (3 drinks or more/day) increases risk *Activity*: sedentary lifestyle
Potential Indications for 24 hour ambulatory blood pressure monitoring
- Borderline HTN - Variable Clinic BPs - Suspected White Coat HTN - Resistant HTN - Eval of symptoms suggesting postural HTN - Prognostic cardiovascular tool
Hypertensive Encephalopathy May Occur in....
- May develop at *diastolic pressures as low as 100 mmHg in previously normotensive patients who have acute hypertension* - May develop in patients with *acute glomerulonephritis (where the BP was previously normal) - May develop in *women with preeclampsia*
Smoking Cessation
- Nicotine may increase SBP & DBP for 15 -30 min. via norepinephrine from adrenergic nerves - Take BP 30 min. after last cigarette - Repeated use can result in elevated BP's for most of the day - Cessation is the most effective, immediate way to reduce CVD risk - Patients must be instructed frequently to quit
Does white coat HTN matter?
- No increase in Cardiovascular morbidity or mortality Increased risk of: - stroke - developing Left Ventricular Hypertophy (LVH) - developing sustained HTN
Terminology
- Systolic Blood Pressure (SBP) = peak BP - DBP = trough BP - CO = cardiac output - SVR = Systemic Vascular Resistance - Mean Arterial Pressure = (SBP + 2DBP)/3 - *MAP of 120/80 = (120 + 160)/3 = 93* - CO = SV (Stroke Volume) x HR - MAP = CO x SVR
High BP Causes...
- elevated BP is responsible for over 60% of cerebrovascular disease and 50% of ischemic heart disease - the higher the BP, the greater the chance of heart attack, heart failure, stroke, and kidney disease.
What Labs to Run for HTN?
1.) *Chemistry profile*: - includes BG (diabetes?), creatinine (CKD?), electrolytes (hypokalemia, metabolic alkalosis suggesting hyperaldosteronism, Cushings?), calcium, uric acid, magnesium, phosphate levels and CBC with plts and RBC smear with LDH to evaluate for TMA if malignant HTN 2.) *Urinalysis* (look for evidence of kidney disease as a cause of HTN), urine albumin to creatinine ratio and dysmorphic RBC's or RBC casts. 3.) Lipids 4.) EKG-looking for LVH (left ventricular hypertrophy) or echocardiogram
Types of Hypertension
1.) *Essential (Primary)*: elevated BP with no identifiable cause ~ 75% patients with HTN lack an identifiable cause 2.) *Secondary*: there's an identifiable disorder associated with the hypertension (he hypertension is due to the underlying abnormality that is increasing the BP) - White Coat HTN - Masked HTN - Hypertensive Emergency - Malignant HTN - Hypertensive Encephalopathy - Hypertensive Urgency
Pathogenesis of Renal Parenchymal Disease (2 Mechanisms)
1.) *Na+ and volume excess*: (↑C0) X SVR = MAP 2.) RAAS - Increased Renin secretion despite increased volume status - Increased Renin activity proportional to increased BP - ACE-I and ARB --> decreased BP
Drug Induced Hypertension
1.) *Vices* Alcohol Cocaine Ecstasy Tobacco Metamphetamines Caffeine (not sustained) 2.) *Iatrogenic and OTC* NSAIDS Steroids Nasal decongestants Oral contraceptives
Adrenal Gland
1.) Aldosterone: Zona Glomerulosa 2.) Cortisol: Zona Fasiculata - excess cortisol (e.g. Cushings disease) --> mineralcorticoid defects, can cause HTN - Cortisol is broken down to Cortisone, which does NOT have mineralcorticoid effects 3.) Androgens: Zona Reticularis 4.) Epi and Norepi: Medulla - excess can cause Pheochromocyotma
Other Variables for Predilection of HTN
1.) Excess angiotensin II activity and resultant mineralocorticoid excess. 2.) Abnormally elevated sympathetic neural activity 3.) Imbalances between vasoconstriction (increased endothelin production) and vasodilatation 4.) Genetic factors (mutation in the sodium channel gene, for example 5.) Diet
In patients with newly diagnosed HTN in whom the BP is NOT markedly elevated, there are 3 goals in the initial evaluation
1.) Identify co-morbidities (diabetes, chronic kidney disease) and other cardiovascular risk factors that may influence pharmacologic treatment ("compelling indications"). 2.) Assess for the impact of the patient's high BP on specific organs (i.e.: "target organ damage") 3.) Identify potential secondary causes of hypertension
4 major general clinical clues that suggest the presence of secondary hypertension
1.) People who develop HTN at the *"wrong" age*: (onset of HTN before puberty, or after age 55). 2.) HTN with *sudden onset* (when previously the BP was normal). 3.) *Resistant hypertension* (failure to achieve control on at least 3 drugs, including a diuretic). 4.) Patients with *an abnormality on history or physical or laboratory examination suggesting a secondary cause* (positive family history, renal bruit, low potassium, Cushinoid facies, etc.).
Non-Dippers
15%-30% of patients with HTN who do not experience a nighttime decrease in BP - more target organ damage - greater risk for future cardiovascular events than dippers. In order to determine if someone is a dipper or non-dipper, one must check BP's 24 hours per day.
Exercise Therapy
3 time/wk for vigorous activity vs.5 times/wk moderate Heart rate monitoring: to identify the HR range that corresponds to an exercise prescription (60-90% of max. HR) *Estimate max. HR by subtracting age from 220* Example 40 year old - Lower limit (220-40) x .60 = 108 bpm - Higher limit (220-40) x .90 = 162 bpm *Physical activity may lower SBP 4-9 mmHg*
Action to Control Cardiovascular Risk in Diabetes (ACCORD)
4700 pts type 2 DM & CVD or 2 risks for CVD randomized SBP 140 vs 120 - SBP's achieved mean 133 vs 119 - After 5 years no sig. difference in primary composite outcomes for nonfatal MI nor in death from CV causes. - Some benefit in reduction of Stroke *Conclusion: BP < 140/90 general population* *BP < 140/90 in diabetics*
Systolic Hypertension in Elderly Program (SHEP)
4736 patients > 60 y/o with mean BP 170/77 Stopped all BP meds: Goal SBP<160 & at least 20mmHg ↓SBP Treated chlorthalidone 12.5 ↑'d to 25mg Atenolol or reserpine was added Mean SBP 143 Benefited all age groups even over 80 both in men and women. Not if hypokalemia the CV events were lost. Only 70% treated reached goal and some on placebo received BP meds. NNT 18
Optimal BP
<115/75
Normal 24hr Average-BP
<130/80 mmHg is probably normal > 135/85 mmHg is probably abnormal
Hypertensive Emergency
Acute, life-threatening events associated with marked increases in BP. 2 major clinical syndromes caused by the severe hypertension: - Malignant hypertension - Hypertensive encephalopathy
KNOW FOR TEST
BP >140/90 is HTN and needs to be treated!!!!
Primary HTN: Salt Sensitivity
BP fluctuations in parallel with changes in salt balance - Natriuretic and anit-natriuretic systems are altered with salt load independent of renal perfusion pressure Strong evidence for genetic links. Ones environmental salt load reveals salt sensitivity BP phenotype. People most likely to be salt sensitive are: - those of *African decent, elderly, obese, diabetic and CKD* If an individual has a blunted response of RAAS to a salt load, they may not waste the Na and then be predisposed to HTN
What BP is Too High?
BP greater than or equal to *140/90*is labeled as hypertension - risk of death from heart disease and stroke begins to rise at BPs as low as 115/75 and that it doubles for each 20 /10 millimeters (systolic over diastolic, respectively) of mercury (mm Hg) increase Pre-hypertension that includes BP between *130-139 systolic and 80-90 diastolic* - vascular changes of thickened arteriolar wall and abnormal responses to constricting and dilating agents are present even when BP is in this "Pre-hypertension" range.
BP Circadian Pattern
BP levels follow a reproducible circadian pattern in patients both with and without HTN - Normally, BP falls during sleep and increases in the early AM. This is followed by variable BP's during the day. The fall in BP during sleep is called "*dipping*".
ABPM (Ambulatory blood pressure monitoring)
BP measured over a 24-hour period (ambulatory BP monitoring, or ABPM) - superior to clinic BP in predicting future cardiovascular events Procedure involves the automated inflation of a BP cuff that is worn for 24 hours - BP's are recorded every 15-20min throughout the day and during sleep, stored in the device and submitted to the MD's office - average day (diurnal) or night (nocturnal) BPs are displayed by a computer
CO and MAP: What Increases these?
CO and MAP increased by increasing SV or HR by high Na diet: Teriyaki sauce - one tablespoon contians 700 mg of sodium Soy sauce - one tablespoon contains 1000 mg of sodium Cocaine acts as a serotonin-NE-dopa reuptake inhibitor Amphetamines increase BP
What Defines Target Organ Damange?
Chronically elevated BP has cumulative detrimental effects on various organs. Chronic target organ damage attributed to HTN is listed below. *Heart* - Left ventricular hypertrophy - Angina/prior myocardial infarction - Heart failure *Brain* - Stroke or transient ischemic attack - Dementia *CKD* - Reduced GFR *Peripheral arterial disease* *Retinopathy*
Role of Dietary K+ in HTN
Diets rich in K+ can lower BP and even lessen the adverse effects of NA on BP - Blacks are especially likely to benefit from an increased intake of potassium - Increased potassium intake lowers BP in non-hypertensive and hypertensive individuals - Estimated that a decrease in K+ intake of 50mmol/day was associated with an increase in systolic pressure of 3.4 mm Hg and an increase in diastolic pressure of 1.9 mm Hg
Pulse Pressure
Difference between the systolic and diastolic BP *Systolic BP*: tends to rise progressively throughout life, and with arteriosclerosis and loss of vascular compliance increase in systolic pressure exceeds that of diastolic pressure increase thus the *Pulse pressure seem to increase with aging* - *High pulse pressure is also a major prognostic factor for cardiovascular risk* - Felt to reflect *increased arterial stiffness due to atherosclerosis*
Hypertension
Disorder of chronically elevated BP Hypertension is a huge public health problem for several reasons: 1.) It is very common 2.) It is often asymptomatic 3.) It has potentially devastating consequences, as it is *one of the most important risk factors for stroke, heart disease, kidney failure and increased risk of death*
Malignant Hypertension = Emergency
Elevated BP with target organ involvement! Target organs 1.) Brain --> Hypertensive Encephalopathy, Stroke 2.) Heart --> MI, CHF, LVH 3.) Kidneys --> Renal Failure, TMA (Thombotic Micrio-Angiopathy = intrinsic kidney diseases that injures arteriole, deposition of platelets etc) 4.) Vasculature --> Aortic Dissection, PAD 5.) Eyes --> Papilledema 6.) Fetus --> Eclampsia *Treat with Fast acting IV meds!!!!*
Role of Dietary Na+ in HTN
Essential hypertension is virtually absent in populations where the individual consumption of sodium chloride is low *Positive correlation between increased Na intake and increased risk of HTN*
Goals of Initial Eval in Pts with Marked Elevation of BP
First priority is to assess for *evidence of target organ damage, and to initiate treatment to control the BP* The evaluation of risk factors, and the evaluation for potential causes of secondary HTN are postponed until the patient is stable.
HTN with Hemoptysis: What diseases could they have?
Goodpasture's Ank-associated Vasculitis ?? *Glomerulonephritis*
Kidneys and Hypertension
HTN is a risk factor for CKD and ESRD - Nephrosclerosis:hyaline accumulation in vessel walls Fibrointimal proliferation of the arcuate artery (In benign HTN, hyaline (pink, amorphous, homogeneous material) accumulates in the wall of small arteries and arterioles, producing the thickening of their walls and the narrowing of the lumens. Consequent ischemia will produce tubular atrophy, interstitial fibrosis, glomerular alterations (smaller glomeruli with different degrees of hyalinization - from mild to sclerosis of glomeruli) and periglomerular fibrosis. (Hematoxylin-eosine, ob. x10)
HTN Epidemiology
HTN prevalence > 65 million people in the US (>140/90) - Prehypertension prevalence is probably another 70 million (120-140 / 80-90) - The BP relationship to risk of CVD is continuous, consistent, and independent of other risk factors.
US Deaths 2012
Heart Disease
VA Cooperative Morbidity Trial in HTN 1967
How does control of Diastolic BP benefit patients? - Randomized placebo vs Thiazide+other agents Treating 3 people prevents a major CV event - No women in the study!
HTN and Heart
Hypertension is the major risk factor for premature cardiovascular disease: LVH Pts. with LVH have increased incidence: - CHF - Ventricular arrhythmias - Myocardial Infarction - Sudden Death
White coat hypertension
If office readings average *>140/90* and out of office readings average *<135/85*, it is sometimes labeled as white coat hypertension. Prevalence of white coat hypertension ranges from 10 to >20 % of pts, and appears to be *more common in children and the elderly* *If the office DBP is > 105, white coat HTN is unlikely*
National Health and Nutrition Examination Survery (NHANES)
Improvement but not 100% yet
Diagnosis of HTN
In the absence of obvious end-organ damage, the Dx of HTN should not be made until the BP has been measured and the *mean of 2 or more properly measured seated BP readings are made each of at least 2 office visits*
Obesity: Pathogenesis of Risk for HTN
Increase in visceral adipocytes --> increased free fatty acids --> increase in *TNF-α, IL-1* - these cytokines may impair insulin signaling which causes *insulin resistance and hyperinsulinemia* leading to *increased SNS activity and HTN* The impaired insulin signaling may also lead to *less insulin receptor activation and less vasorelaxation* [Do NOT need to remember this!! Theorized only!!]
Which is more important - Systolic or Diastolic BP?
Increased values of either is a predictor of poor cardiovascular outcome and mortality - Systolic BP appears to be as major a risk factor for cardiovascular disease as is Diastolic pressure
Etiology of HTN Secondary Causes
Kidney - Glomerulonephritis/kidney disease - Renovascular disease Endocrine - Hyperaldosteronism - Pheochromocytoma - Cushing's syndrome/Steroid therapy - Acromegaly - Thyroid/parathyroid diseases - Carcinoid tumors - Other Sleep apnea - Drug induced/related - Coarctation of aorta
How to think of medication use.
MAP = CO x SVR CO = SV x HR (volume vs contractility) SVR = Vasoconstriction 1.) *HTN due to Volume --> use Diuretics* 2.) *HTN due to Vasoconstriction --> Use* - *Renin: ACE-I or ARB, B-blockers* - *Non renin: CCB (calcium channel blockers) -dihydropyridines*
Hypertensive Encephalopathy
Marked elevation in BP accompanied by neurologic symptoms Neurologic symptoms, which are related to cerebral edema, (a result of hyperperfusion from severe and sudden rises in BP) are characterized by headache, nausea, vomiting, restlessness, and confusion - If untreated may progress to seizures and coma
Dietary Approaches to Stop Hypertension Study (DASH)
Multicenter trial comparing typical American diet vs. Diet emphasizing.... 5 servings each of Fruits and Vegetables a day and Whole Grains STUDY: 460 healthy men & women mean age 44 - SBP < 160 and DBP < 80 - 95 - African Americans (AA) 60%, Hypertensive patients 29% --> BP reductions greatest in AA and in hypertensives with BP decreased 11.4/decreased 5.5 mmHG for DASH diet in hypertensives
Why SBP<140?
No good prospective studies aiming for SBP<140 Used because of epidemiologic risk Mean SBP in SHEP (Systolic Hypertension Elderly Program) 143
Classification of HTN
Normal: Below 120/80 Prehypertension: 120-139/80-89 Stage 1 Hypertension: 140-159/90-99 Stage 2 Hypertension: Above 160/100
How do you evaluate patients suspected of having secondary HTN?
Pic
Clinical and Biochemical Characteristics of Salt Sensitive BP
Pic - if BP goes up on High Na diet, they are probably Salt Sensitive
Primary HTN: Aging
Prevalence of HTN increases as we age Composition of the arterial wall structure depends on the *composition of the middle layer, the tunica media, and the degree of elastin versus collagen*: - Young healthy people have *more elastin in the media of the aorta* and this decreases further out in the periphery - Aging also affords other insults with humoral factors and oxidative metabolites that play a role in arteriosclerosis
Masked Hypertension
Pts are normotensive by conventional clinic measurement, but are hypertensive when evaluated by *ambulatory blood pressure monitoring (ABPM)* - Associated w/ an increased risk of sustained HTN and cardiovascular morbidity in some studies --> careful monitoring for the development of sustained HTN and cardiovascular morbidity
Impact of Pre-Hypertension
Pts with prehypertension: - more likely to progress to sustained HTN - increase in cardiovascular risk
Liddle's Syndrome
Rare autosomal dominant condition in which there is an *increase in both collecting tubule NA reabsorption and K+ secretion*. Genetic abnormality involves the collecting tubule Na channel --> marked increase in Na transport and loss of inhibition of channel activity Disorder is associated with *hypertension, low plasma renin and aldosterone levels, hypokalemia, and metabolic alkalosis*
Benefits of Lowering BP [KNOW THIS]
Reductions in: Myocardial infarction 25% Stroke incidence 35% Heart failure 50%
Primary HTN: Obesity
Risk Factor for DM, CVD and HTN - Degree of abnormal body mass index, BMI, along with waist circumference increases the risk > 85% of people with HTN have a BMI > 25 - Majority of patients with HTN are overweight - HTN is approximately *6x more frequent in obese than in lean subjects* - Weight gain in young people is a potent risk factor for development of HTN - For every *10 kg increased weight this increases SBP and DBP by 3 and 2.3 mmHg respectively* (be sure to know bolds!)
Primary Aldosteronism
Secondary cause of HTN from Adenoma or Hyperplasia of the Adrenal Gland - Excess Aldosterone inhibits Renin level --> *High Aldo:Renin Ratio* - Pts have *Resistant HTN*
Pheochromocytoma
Secondary cause of HTN from Rena Medulla tumors causing excess Epi/Norepi release; "tumor of adrenaline" 1.) Rare 2.) Symptoms/Signs - Headache - Palpitations - Diaphoresis - HTN - may be sustained or paroxysmal 3.) Diagnosis - *urinary metanephrines & normetanephrines*
Hypertensive Urgency
Severe hypertension (diastolic blood pressure above 120 mmHg) in patients who are asymptomatic
BP Goals
Targets: BP < 140/90 general population BP < 140/90 in diabetics KNOW THIS Determined by the ACCORD Study
Secondary cause of HTN: Renovascular Hypertension
Types: 1.) *Arteriosclerosis* 80% Ischemia --> increased RAAS --> Aldosteronism - damage to muscle in blood vessel leads to beading - not just isolated in kidneys - mostly in women but also in men - *Abdominal pain on eating* 2.) *Fibromuscular Dysplasia* 20%
Primary HTN: Etiology and Risk Factors
Usually no obvious cause of their HTN Risk factors: - Genetics - Low Birth Weight - Aging - Obestiy - Salt Sensitivity
Autoregulation of Blood Flow (BF)
VITAL for brain and kidney blood flow - Autoregulation to brain and kidneys via hormones (Catecholamines, Angiotensin II, etc) Autoregulatory range is shifted to higher pressures in patients with HTN due to an increase in vascular tone and thickened arteriole walls -->leads to vessel damage, vessel leakage, vessel muscle thickening - hard to tolerate lower BPs once curve has shifted - too high BP --> hemorrhagic stroke
Using Treatment Dx the Cause of HTN
When obvious cause to HTN not uncovered through history, exam or diagnostic eval, management may uncover the reason Break down the reason we have HTN simplistically into two factors: *BP = Cardiac Output (CO) x Systemic Vascular Resistance (SVR)* - can isolate the cause by *managing CO or SVR* *CO = Stroke Volume (SV) x HR* 1.) Use diuretics to lower SV and therefore CO. 2.) If that fails, we can then use vasodilators to reduce vasoconstriction that may be elevating the SVR 3.) May use a combination of the two
HTN in Young vs Old
Young ppl with HTN have higher Diastolic due to more elastin in aorta (aorta contracts) Ppl >60 Elastin becomes collagen --> with age Diastolic BP gets lower
Malignant hypertension
a complication of HTN characterized by *very elevated BP and end organ damage in the eyes, brain, lung and/or kidneys* - Accompanied by *papilledema (swelling of the optic nerve), or retinal hemorrhages and exudates* Usually associated with a *diastolic pressure >120 mmHg* - Often occurs in patients with *long-standing uncontrolled HTN* or who have *discontinued their antihypertensive therapy*
Chronically Elevated BP...
affects the entire body by causing *changes to the endothelium and muscular layer of the arterioles that leads to impaired blood flow to various organs and also results in atherosclerosis*. Complications of hypertension and the accompanying atherosclerotic disease include *damage to the brain, heart, kidneys, eyes and peripheral blood vessels* - elevated BP is responsible for over 60% of cerebrovascular disease and 50% of ischemic heart disease
Effect of BP Control
as small as 2 mm Hg reduction in diastolic BP reduces the risk of coronary heart disease and stroke by 7 and 15% respectively - the lower the treated BP the greater is the reduction in these complications.
Primary HTN: Low Birth Weight
associated w/ reduced nephron mass and increase risk of HTN In utero kidney development is mature at 36 weeks - Low glomerular number may lead to *glomerular hyperfiltration, glomerulosclerosis and microalbuminuria* - Low birth weight or prematurity leading to HTN or CKD is circumstantial evidence
Essential (Primary) HTN
elevated BP with no identifiable cause ~ 75% patients with HTN lack an identifiable cause
2 Methods to Combat HTN in CKD
eliminate Na Block RAAS KNOW THIS
Elastin
has a half life of about 40 years and fatigue of elastin fibers from accumulated stress of more than 2 billion heart beats with aortic expansions by the age of 60 may lead to eventual fracture and disarray of elastin accompanied by changes of the matrix to proliferation of collagen and calcium.
High Risk Patients Should Lower Their BP to...?
high risk patients such as those with diabetes with kidney disease or those with kidney disease and significant protein loss in the urine should have their BP lower to *at least <130/80 level* (not just below 140/90).
Primary HTN: Genetics
in addition to discovered genetics links, individuals with one or both parents with HTN have twice the risks of having HTN
Drugs Associated with HTN
pic
Secondary HTN
there is an identifiable disorder associated with the hypertension; i.e., the hypertension is due to the underlying abnormality that is increasing the BP.
Catecholamine Receptors on Cardiovascular System
α - 1,2 Receptors --> Bind (NE>EPI) ↑Vasoconstriction β Receptors --> Bind (EPI>NE) β 1 - ↑ Heart Rate and Contractility β 2 - ↑ Vasodilatation
Physical Exam of Pt with HTN
• Accurate evaluation of BP, with verification in both arms and a leg • If the BP is not equal bilaterally or lower in the leg- think coarctation of aorta • Determination of weight to assess BMI (body mass index) • Evaluation for end organ damage- Eye exam-evaluate for hypertensive retinopathy (retinal artery narrowing, leaking of blood causing intra-retinal hemorrhage) Heart -left ventricular hypertrophy • Thyroid exam, carotid bruit • Cardiac exam: size, rhythm, and sounds, presence of LVH, peripheral pulses • Abdomen-renal masses, renal bruits, femoral pulses and peripheral pulses, aortic aneurysm • Neuro exam-hypertensive encephalopathy (confusion, headache, seizures), cranial nerves, muscle tone, reflexes
Acute evidence of target organ damage includes:
• Chest pain (myocardial infarction, unstable angina) • Acute heart failure • Neurologic symptoms (stroke, encephalopathy, confusion) • Visual disturbances and on eye exam papilledema • Acute kidney injury • Thrombotic Microangiopathy (TMA) with hemolysis and thrombocytopenia with brain and kidney involvement An assessment for these symptoms/signs should be performed in all patients presented with markedly elevated blood pressure.
