B P4 C26 Systemic Hypertension: Mechanisms, Diagnosis, and Treatment Flashcards
After tobacco use and diabetes, ____ is the most important risk factor for peripheral vascular disease (the second leading cause of loss of limbs in the United States).
Uncontrolled primary hypertension
_____ is the most important modifiable risk factor for stroke, the leading contributor to all common forms of heart failure, the second most common cause of end-stage kidney disease, and also contributes to memory loss.
Uncontrolled primary hypertension
More recent guidelines, however, define the level at which one is considered hypertensive based on level of cardiovascular (CV) risk rather than just the BP number. This is true of the most recent US guidelines that define hypertension as _____ mm Hg and the European Guidelines which use a slightly different approach to risk and define hypertension as _____ mm Hg
US: ≥130/80
EU: ≥140/90
The traditional “threshold BP value” to secure a diagnosis of hypertension comes from large epidemiologic studies demonstrating a higher mortality at levels above _____ mm Hg.
140/90
A natural history study involving almost 12,000 veterans, followed over 15 years, noted that BP level correlated with risk for end-stage kidney disease. Note that, in this study, the highest risk for end-stage kidney disease was found at levels above the renal autoregulatory range (i.e.,a systolic BP >_____ mm Hg)
> 180 mm Hg
A natural history study of over a million people demonstrates that CV risk becomes most pronounced above levels of _____ mm Hg
140/90
In the Framingham study the lifetime risk of 55- to 65-year-old men or women for developing hypertension was above ___%.
> 90%
These data highlight the public health importance of SBP, particularly among people older than 50 years of age. In such individuals, _____ is a much better predictor of hypertensive target-organ damage and future CV and renal events than is DBP.
SBP
Levels defining hypertension according to the ACC/AHA
Office/clinic BP: ≥130/≥80
Daytime mean: ≥130/≥80
Home BP mean: ≥130/≥80
24-hr mean: ≥125/≥75
Nighttime mean: ≥110/≥65
Levels defining hypertension according to the ESC/ESH
Office/clinic BP: ≥140/≥90
Daytime mean: ≥135/≥85
Home BP mean: ≥135/≥85
24-hr mean: ≥130/ ≥80
Nighttime mean: ≥120/≥70
As a result, interpretation of BP levels in children and adolescents usually involves comparison of a child’s average BP (from three visits) to a comprehensive table that provides thresh- old values for “elevated” (traditionally, BP between the _____ percentiles), “hypertension” (BP between the _____ percentiles),and “severe hypertension” (____ percentile or higher).
Elevated: 90-95th
Hypertension: 95-99th
Severe Hypertension:>99th
The factors that generate BP comprise the integration of cardiac output (CO) and systemic vascular resistance (SVR): BP = CO × SVR.
Note that CO =_____; SVR = _____.
BP = CO × SVR.
CO = heart rate × stroke volume
SVR = 80 × (MAP − CVP)/CO
Pressure natriuresis is defined as:
The increase in renal sodium excretion due to mild increases in BP, typically because of extracellular fluid volume expansion, allowing BP to remain in the normal range
The evaluation of patients with hypertension focuses on six key components:
(1) Confirmation that the patient is indeed hypertensive through careful measurements of BP;
(2) Assessment of clinical features that might suggest specific remediable causes of hyper- tension;
(3) Identification of comorbid conditions that confer additional CV risk, or that may impact treatment decisions;
(4) Discussion of patient-related lifestyle factors and preferences that will affect management;
(5) Systematic evaluation of hypertensive target-organ damage;
(6) Shared decision making about the treatment plan
High BP is typically asymptomatic, but some symptoms are common among patients with very high BP levels, such as headaches, epistaxis, dyspnea, chest pain, and faintness, all of which were present in more than 10% of patients presenting with DBP levels above ____ mm Hg.
120 mm Hg
Lastly, some non-CV conditions may have an impact on treatment options. For example, patients with reactive airways disease (asthma) probably should not receive _____, patients with prostatic hyperplasia may benefit from a regimen that includes an _____, and patients with attention-deficit/hyperactivity disorder or anxiety may benefit from a _____ (e.g., guanfacine), whereas those with major depression should probably not be treated with this drug class.
Nonspecific BB
Alpha blocker
Central sympatholytic
Focus should be on the development of hypertension at a young age or clustering of endocrine (_____) or renal problems (_____).
Pheochromocytoma, MEN, primary aldosteronism
PCKD or any inherited form of kidney disease
The physical examination is designed to complement the items dis- cussed in the history.One should pay attention to syndromic features of _____(moon face,central obesity,frontal balding,cervical and supraclavicular fat deposits, skin thinning, abdominal striae), _____ (tachycardia, anxiety, lid lag/proptosis, hypertelorism, pretib-al myxedema), _____(bradycardia, coarse facial features, macroglossia, myxedema, hyporeflexia), _____(frontal bossing, widened nose, enlarged jaw, dental separation, acral enlargement, car- pal tunnel syndrome), _____(neurofibromas, café au lait spots, as neurofibromatosis is associated with pheochromocytoma and renal artery stenosis), or _____ (hypopigmented ash leaf patches, facial angiofibromas, as tuberous sclerosis is associated with renal hypertension, usually related to angiomyolipomas).
Cortisol excess
Hyperthyroidism
Hypothyroidism
Acromegaly
Neurofibromatosis
Tuberous sclerosis
A _____ should be considered in younger patients with unexplained, difficult-to-treat hypertension and is evaluated by measurement of BP in both arms and in one thigh. If present, there will be a significantly lower BP in the thigh (typically by more than ___ mm Hg).
Coarctation of the Aorta
30 mm Hg
Sometimes, in case of a CoA lesion proximal to the left subclavian, there may be a significant interarm BP difference, lower on the _____. In addition, there is significant decrease in intensity of the femoral pulses and a palpable radial-femoral pulse delay.
Left
A funduscopic examination is recommended to evaluate for vascular changes associated with hypertension, especially if present for a long period of time (i.e.,greater than _____ years).The retinal changes are associated with severity of both acute and chronic BP elevation.
5-10 years
Acute retinal changes can happen quite abruptly (hours to days) and range from arteriolar spasm in most patients with uncontrolled BP to retinal infarcts (exudates) and microvascular rupture (flame hemorrhages), to _____ once the protection afforded by vasoconstriction is overcome.
Papilledema
_____ retinal changes take much longer to develop and include vascular tortuosity (arteriovenous nicking) due to perivascular fibrosis, followed by progressive arteriolar wall thickening that prevents visualization of the blood column, thus leading to the appearance of copper wiring, then silver wiring.
Chronic
The CV examination focuses on the identification of _____ (jugular venous distension, lung crackles, edema), _____ (deviated cardiac impulse), and the presence of a third or fourth heart sound as markers of ______.
Volume overload
Cardiac enlargement
Impaired LV compliance
______ can be identified by the presence of bruits over the carotid arteries, as the prevalence of carotid atherosclerosis is increased in patients with hypertension, as well in the abdomen, primarily looking for renal arterial bruits heard over the epigastrium and/or flanks.These bruits are of greater significance if occurring on both systole and diastole.
Subclinical atherosclerosis
_____-based brachial BP is the most used method to measure BP, typically in the office setting.
Cuff- based
Most patients should have their BP measured in the arm while in the _____ position. Once an arm is selected it should always be used for subsequent BP readings.
Seated
Aneroid and electronic oscillometric manometers are accurate but should have periodic maintenance (every __ months) to ensure that they are properly calibrated, as well as any time poor function is suspected.
12 months
When assessing BP on the initial visit, _____ BP should be obtained, especially among older patients, in whom it occurs in 8% to 34% of patients.
Orthostatic BP
The phenomenon of _____ hypertension is defined as a clinical condition in which a patient’s office BP level is normal but ambulatory or home BP readings are in the hypertensive range.
Masked hypertension
Orthostatic vital signs (heart rate and BP) are best obtained after at least _____ minutes in the supine position followed by immediate assumption of the standing position, when sequential measurements are taken for up to _____ minutes.
Supine: after 5 min
Sequential measurements: up to 3 mins
To account for this fact, a fall of _____ mm Hg may be used for the definition of orthostatic hypotension when the test is performed using the seated BP as baseline as compared with the generally accepted definition of orthostatic hypotension as a drop in BP of more than ________ that occurs after 3 minutes of standing
Seated BP as baseline: 15/7 mm Hg
General definition: > 20/10 mm Hg after 3 mins of standing
In the past 30 years, _____ have become accepted as better markers of hypertensive target-organ damage and adverse clinical outcomes.
ABPM and Home BP
_____ BP monitoring has stronger associations with LVH, albuminuria, kidney dysfunction, retinal damage, carotid atherosclerosis, and aortic stiffness than office BP, although this is not consistent among studies.
ABPM
Likewise, _____ BP is a better marker than office BP for LVH and proteinuria, though it is not consistently superior for other measures of target-organ damage.
Home BP
In the assessment of hard CV endpoints, _____ BP has consistently outperformed office BP in studies that account for the values observed in the office; in other words, no matter what the office BP, it is the out-of-office BP that decisively drives outcomes
Out-of-office BP
In meta-analyses of studies that evaluated both office and ABPM on outcomes, only _____ values retained significance and was useful in masked hypertension
ABPM
The normal circadian BP pattern includes a fall in BP of approximately _____% during sleep. Patients who lack this normal BP dip during sleep are called “nondippers” (arbitrarily defined as a sleep BP that falls by less than __% compared with awake levels) and have increased target-organ damage and overall CV risk.
Normal dip: 15-20%
Nondippers: < 10%
In large observational studies, patients whose SBP falls by ___% or more during the night have lower fatal and nonfatal CV event rates than those whose BP decreases by less than 20%, whereas those whose BP does not fall at all during the night have significantly worse CV outcomes than all other patients
> 20% SBP fall during the night = lower fatal and nonfatal CV event rates
Although not feasible in many clinical settings, 24-hour ABPM is recommended for all newly diagnosed individuals with hypertension to eliminate the diagnosis of:
WCH
Masked hypertension
Evaluate dipping status while sleeping
A typical measurement interval in ABPM is every _____ minutes during the daytime (7 AM to 11 PM) and every _____ minutes at night (11 PM to 7 AM), although the frequency and time windows can be adjusted based on clinical needs, such as the need to identify frequent BP swings, atypical sleep patterns, etc
Daytime: 20 mins
Nighttime:: 30mins
It is used commonly in clinical practice and is associated with improved adherence to therapy. It has been used successfully for self-titration of BP medications and is amenable to telemedicine approaches, in which the patient can upload BP values via telephone or direct entry to a Web server so that clinicians can inspect the BP logs and make treatment decisions remotely.
Home BP
Key steps for proper blood pressure measurement
- Properly prepare the patient (e.g., quiet area, seated in chair, back firmly supported and feet flat on the ground, arm supported with appropriately size cuff placed). Wait 5 min, then check BP three times 1 min apart. Eliminate the first reading and average the next two readings.
- Provide BP readings to patient.
- Selection of proper cuff size as a function of arm circumference
Selection of proper cuff size as a function of arm circumference:
22-26cm: Small adult
27-34cm: Adult
35-44cm: Large adult
45-52cm:Adult thigh
_____ cuffs often provide incorrect readings because of inappropriate technique but, if used correctly, can be convenient and accurate, and particularly useful in obese patients.
Wrist cuffs
_____ cuffs are inaccurate and should not be used.
Finger cuffs
To allow management decisions, home BP monitoring is best performed using specific periods of monitoring. For most patients, a BP log obtained over _____ days before each office visit suffices because it retains excellent reproducibility.
7 days
To allow management decisions, home BP monitoring is best performed using specific periods of monitoring.For most patients, a BP log obtained over 7 days before each office visit suffices because it retains excellent reproducibility. We recommend that the patient obtain readings in duplicate (approximately _____ minute apart), twice daily (in the morning before taking medications and in the evening before dinner)
Duplicate readings 1 min apart 2x a day
The ACC/AHA guidelines recommend the use of out-of-office BP to evaluate patients who are receiving treatment for hypertension but remain above goal in the office, with the explicit caveat that the recommendation is based on expert opinion. The high prevalence (approximately 40% to 51%) of a _____ in patients with resistant hypertension supports this recommendation.
White coat effect
Patients with office BP above _____mm Hg do not need further confirmation of hypertension and should be treated.
160/100 mm Hg
In the absence of worrisome signs or symptoms during the initial evaluation, a basic set of tests include:
Renal function
Electrolytes
Calcium
Glucose
Hemoglobin
Lipid profile
Urinalysis
Electrocardiogram
Patients who are resistant to treatment during follow-up have higher rates of secondary causes of hypertension, in particular _____, thus deserving a more dedicated search for secondary causes in their evaluation.
Sleep apnea
Hyperaldosteronism
Renovascular disease
_____ is the most common target-organ damage in hypertension and is independently associated with worse prognosis, marked by increased risk for CV events (coronary, cerebrovascular), heart failure, and death.
LVH
The prevalence of LVH among patients with hypertension is approximately ___% based on electrocardiographic criteria, whereas this number increases to approximately ___% when more sensitive echocardiographic criteria are used.
ECG: 18%
Echo: 40%
The echocardiogram provides information on _____ which is often impaired early in the course of hypertensive heart disease even in the absence of LVH
LV diastolic function
Because of the importance of sodium and potassium as dietary interventions in hypertension, it is often useful to quantify intake objectively. A _____ for electrolytes can be performed on a patient on a stable dose of a diuretic.It is important to not allow hypokalemia, because that will increase BP
24-hour urine collection
The evaluation of _____ activity has been proposed as an empiric method for the evaluation and treatment of hypertension
Plasma renin activity
The evaluation of plasma renin activity has been proposed as an empiric method for the evaluation and treatment of hypertension. The premise for this approach is mechanistic: patients with high plasma renin activity levels (_____ ng/mL/hr, and particularly _____ng/mL/hr) have vasoconstriction mediated by the RAAS as the primary operative mechanism of hypertension, whereas those with suppressed plasma renin activity levels (_____ ng/ mL/hr) are volume overloaded
Vasoconstricted: >0.65 ng/mL/hr, particularly >6.5 ng/mL/hr
Overloaded: <0.65 ng/mL/hr
Accordingly, patients with high levels of plasma renin activity are treated with blockers of the _____, and those with low levels of renin are treated with _____.
High renin: RAAS
ACEIs/ARBs
Renin inhibitors
Beta blockers
Low renin:
Diuretics (including aldosterone antagonists)
Calcium channel blockers (CCBs)
Alpha blockers
Renin profiling is rarely used, and a good history and physical are as reliable as renin profiling; however, it is reasonable to entertain renin profiling, especially in patients who _____.
Do not respond to initial therapy
The most common cause of secondary hypertension is _____, accounting for approximately 20% to 25% of all secondary hypertension cases.
Primary hyperaldosteronism
_____ disease are two common nonendocrine causes of resistant hypertension. Additional factors contributing to resistance include dietary issues around sodium and potassium as well as commonly used over-the-counter medications.
Coarctation of the aorta and renovascular disease
Primary hyperaldosteronism as a form of secondary hypertension has been increasing in prevalence worldwide over the past 25 years and is generally due to one of six subtypes:
(1) Aldosterone-producing (“Conn”) adenoma, nearly always in one adrenal gland (approximately 35% of cases);
(2) Bilateral adrenal hyperplasia (also known as “idiopathic primary hyperaldosteronism,” approximately 60% of cases);
(3) Primary (or unilateral) adrenal hyperplasia (approximately 2% of cases);
(4) Aldosterone-producing adrenal carcinoma (approximately 35 cases in the world’s literature);
(5) Familial hyperaldosteronism, which takes one of two forms: glucocorticoid- suppressible hyperaldosteronism, due to a chimeric chromosome 8, in which the 5%-regulatory sequence for corticotropin responsiveness of 11à-hydroxylase is fused to the enzyme-coding sequence for aldosterone synthase (<1% of cases), or familial occurrences of either an aldosterone-producing adenoma or bilateral adrenal hyperplasia (<2% of cases);
(6) Ectopic production of aldosterone by an adenoma or carcinoma outside the adrenal gland (<0.1% of cases).
In addition, obstructive sleep apnea (OSA) and sleep-disordered breathing also cause hyperaldosteronism. This is classically described as _____, but its evaluation and medical treatment are often quite similar to that of bilateral adrenal hyperplasia.
Secondary hyperaldosteronism
Primary hyperaldosteronism appears to be more common in people with:
(1) Higher levels of BP (2% for BP levels 140 to 159/90 to 99 mm Hg,8% for BP levels 160 to 179/100 to 109 mm Hg, and 13% for BP levels >180/110 mm Hg)
(2) Treatment-resistant hypertension (17% to 23% in several series)
(3) Patients with hypertension with either spontaneous or diuretic-associated hypokalemia
(4) Hypertension with a serendipitously discovered adrenal mass (1% to 10%).
In the last millennium, hypokalemia was thought to be very common (if not nearly universal) among patients with primary hyperaldosteronism, particularly if provoked by diuretic therapy. Today, however, more afflicted patients have ______, although sometimes more severe cases have weakness, muscle cramps, and even periodic paralysis.
Eukalemia than hypokalemia
Screening for primary hyperaldosteronism is most efficiently performed in potassium-repleted patients, using the ______.
Ratio of plasma aldosterone concentration to plasma renin activity (ARR)
The ARR can be affected by many factors, including _____ as well as a number of agents that can confound the diagnosis of true hypertension
Antihypertensive drug therapy
Dietary sodium restriction
Posture
Time of day
Sample handling
The likelihood of a false-positive ARR is increased by a _____, so some investigators require the plasma aldosterone concentration to be above a given threshold (e.g., >___ ng/dL), for the screening to be considered positive, but levels between 12 and 15 ng/dL need to be considered individually, as some patients with proven aldosteronism have values in this range.
Low plasma renin activity (e.g., <0.5 ng of angiotensin II per milliliter per hour)
Screening: Aldosterone >15 ng/dL
The most common cutoff value for an ARR that usually leads to further investigation is __ (when aldosterone level is measured in nanograms per deciliter and plasma renin activity in nanograms of angiotensin II per milliliter per hour),but higher thresholds lead to more falsely negative tests.
ARR 30
The traditional “Saline-loading test” (2 L infused over 4 hours) is confirmatory if the postinfusion plasma aldosterone concentration is greater than ___ ng/mL. Patients with aldosterone concentrations between 5 and 10 ng/mL are considered indeterminate and should be retested. Note, intravenous saline is not often recommended for patients with heart failure, CKD, or uncontrolled hypertension.
> 10 ng/mL
Many centers have reported success with an oral sodium-loading protocol, which involves _____.The test is considered positive if the urinary aldosterone excretion is greater than _____μg/day, but oral sodium loading can be as problematic in some patients as intravenous saline.
Liberalizing sodium intake to approximately 6 g/day for 3 to 5 days and then assaying 24-hour urine collections for sodium (to ensure loading) and aldosterone content
12 to 14 μg/day
The fludrocortisone suppression test involves giving 0.1 mg of fludrocortisone every 6 hours for 4 days, and then assaying the plasma aldosterone concentration when the patient is standing upright. It is considered confirmatory if the concentration is greater than _____ng/dL and plasma renin activity and serum cortisol levels are _____. Execution of the test may be difficult for patients who have a long journey to the office or who are nonadherent.
FST
Aldosterone > 6 ng/dL
Plasma renin: Low
Serum Cortisol: Low
Lastly, the captopril challenge test is performed by assaying the plasma aldosterone concentration before and 1 and 2 hours after administration of 25 to 50 mg of oral captopril. It is considered confirmatory if the plasma aldosterone concentration remains _____ , but many false-negative and equivocal captopril challenge test results have been reported.
Aldosterone: elevated (and unchanged form baseline)
After the diagnosis of primary aldosteronism is confirmed, a _____ of the adrenals is undertaken, which is useful in detecting large masses that might be adrenal carcinomas.
CT scan
Because CT scans identify unilateral adrenal disease with a sensitivity of only 78% and specificity of only 75%, the Endocrine Society recommends adrenal venous sampling for most surgical candidates.
Despite being invasive, expensive, technically challenging, and potentially dangerous and requiring an experienced and well-coordinated team, it has a sensitivity and specificity of 95% an 100%,respectively, for detecting unilateral aldosterone production.
It is commonly performed at 8 AM, with continuous cosyntropin administration, and simultaneous adrenal vein cortisol level measurement.
Most centers use a ____ cutoff value of the cortisol-corrected aldosterone ratio (i.e., the ratio between the aldosterone/cortisol ratios on each side) to define a positive lateralization.
4:1
Laparoscopic procedures for unilateral adrenalectomy have improved to the point that most patients with adrenal venous sampling–proven hyperaldosteronism have shorter hospital stays, fewer complications, and lower costs than open procedures.
Although nearly all return to eukalemia, hypertension is “cured” (i.e.,follow-up BP levels of less than 140/90 mm Hg without antihypertensive drug therapy) in only approximately ___%.
“Cure” is more likely in _____. Typically, plasma aldosterone concentration and plasma renin activity are measured shortly after successful surgery, and potassium supplementation and aldosterone antagonists are discontinued. Intravenous saline is often required because the remaining adrenal gland needs to recover its normal function, which may take a few weeks
50%
Younger people
Short duration of hypertension
Prior BP control w/ only 1 or 2 agents
A pedigree that includes <2 two first-degree relatives with hypertension
The nonsurgical option for patients with idiopathic hyperaldosteronism is the aldosterone antagonist _____, which has significantly better efficacy than its successor, eplerenone.
Spironolactone
Most physicians use _____ for glucocorticoid-remediable hyperaldosteronism, but the doses are kept low to avoid iatrogenic Cushing syndrome.
Dexamethasone or prednisone at bedtime (over twice-daily hydrocortisone)
The association of sleep-disordered breathing and hyperaldosteronism is thought to account for approximately 20% of resistant hypertension and typically responds well to selective aldosterone antagonists such as _____.
Spironolactone
_____ is the “gold standard” test for OSA diagnosis but requires overnight evaluation and is expensive.
Polysomnography
A pheochromocytoma is a rare catecholamine-secreting tumor that arises from the _____ cells of the adrenal medulla.
Chromaffin cells
Approximately 90% of pheochromocytomas arise in the ______, 10% of patients have > ____ tumor, and 10% are ______.
90% adrenal gland
10% > 1 tumor
10% malignant
A pheochromocytoma may cause a nonischemic cardiomyopathy secondary to the impact of the _____ on the heart.
Catecholamines
Approximately _____% of patients with von Hippel-Lindau disease type 2 (retinal and/or cerebellar hemangioblastomas, occasionally with clear cell renal carcinoma, pancreatic neuroendocrine tumors, retinal angiomas or hemangioblastomas, mediated by the VHL tumor suppressor gene, located on chromosome 3p25-26) will have pheochromocytomas or paragangliomas.
20%
Selective serotonin reuptake inhibitors (SSRIs) and serotonin- norepinephrine reuptake inhibitors (SNRIs) can increase BP modestly, but some patients receiving _____ may have a severe hypertensive response. Interestingly, when these medications are used for hypertensive patients with depression, BP often improves as depressive symptoms improve
SNRIs
Nonpharmacologic intervention with highest BP lowering effect
DASH -11mm Hg
________ actions are opposite to those of angiotensin II, including vasodilatory and antiproliferative properties that are mediated by the Mas receptor, a G protein–coupled receptor that, upon activation, forms complexes with the AT1 R, thus antagonizing the effects of angiotensin II.
Angiotensin 1 to 7 formed primarily though the hydrolysis of angiotensin II by ACE2
ACE2 expressed largely in the heart, kidney, and endothelium
Effect of sympathetic stimulation in HPN
Vasoconstriction
Salt sensitivity - catecholamine induced hypertension causes renal interstitial injury that associates with a saltsensitive phenotype even after sympathetic overactivity is no longer present
Endothelial dysfunction - enhanced SNS activity results in α1-receptor mediated endothelial dysfunction, vasoconstriction, vascular smooth muscle proliferation, and arterial stiffness
