B P4 C26 Systemic Hypertension: Mechanisms, Diagnosis, and Treatment Flashcards
(213 cards)
1
Q
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).
A
Uncontrolled primary hypertension
2
Q
_____ 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.
A
Uncontrolled primary hypertension
3
Q
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
A
US: ≥130/80
EU: ≥140/90
4
Q
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.
A
140/90
5
Q
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)
A
> 180 mm Hg
6
Q
A natural history study of over a million people demonstrates that CV risk becomes most pronounced above levels of _____ mm Hg
A
140/90
7
Q
In the Framingham study the lifetime risk of 55- to 65-year-old men or women for developing hypertension was above ___%.
A
> 90%
8
Q
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.
A
SBP
9
Q
Levels defining hypertension according to the ACC/AHA
A
Office/clinic BP: ≥130/≥80
Daytime mean: ≥130/≥80
Home BP mean: ≥130/≥80
24-hr mean: ≥125/≥75
Nighttime mean: ≥110/≥65
10
Q
Levels defining hypertension according to the ESC/ESH
A
Office/clinic BP: ≥140/≥90
Daytime mean: ≥135/≥85
Home BP mean: ≥135/≥85
24-hr mean: ≥130/ ≥80
Nighttime mean: ≥120/≥70
11
Q
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).
A
Elevated: 90-95th
Hypertension: 95-99th
Severe Hypertension:>99th
12
Q
The factors that generate BP comprise the integration of cardiac output (CO) and systemic vascular resistance (SVR): BP = CO × SVR.
Note that CO =_____; SVR = _____.
A
BP = CO × SVR.
CO = heart rate × stroke volume
SVR = 80 × (MAP − CVP)/CO
13
Q
Pressure natriuresis is defined as:
A
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
14
Q
The evaluation of patients with hypertension focuses on six key components:
A
(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
15
Q
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.
A
120 mm Hg
16
Q
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.
A
Nonspecific BB
Alpha blocker
Central sympatholytic
17
Q
Focus should be on the development of hypertension at a young age or clustering of endocrine (_____) or renal problems (_____).
A
Pheochromocytoma, MEN, primary aldosteronism
PCKD or any inherited form of kidney disease
18
Q
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).
A
Cortisol excess
Hyperthyroidism
Hypothyroidism
Acromegaly
Neurofibromatosis
Tuberous sclerosis
19
Q
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).
A
Coarctation of the Aorta
30 mm Hg
20
Q
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.
A
Left
21
Q
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.
A
5-10 years
22
Q
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.
A
Papilledema
23
Q
_____ 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.
A
Chronic
24
Q
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 ______.
A
Volume overload
Cardiac enlargement
Impaired LV compliance
25
______ 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
26
_____-based brachial BP is the most used method to measure BP, typically in the office setting.
Cuff- based
27
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
28
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
29
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
30
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
31
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
32
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
33
In the past 30 years, _____ have become accepted as better markers of hypertensive target-organ damage and adverse clinical outcomes.
ABPM and Home BP
34
_____ 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
35
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
36
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
37
In meta-analyses of studies that evaluated both office and ABPM on outcomes, only _____ values retained significance and was useful in masked hypertension
ABPM
38
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%
39
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
40
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
41
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
42
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
43
Key steps for proper blood pressure measurement
1. 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.
2. Provide BP readings to patient.
3. Selection of proper cuff size as a function of arm circumference
44
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
45
_____ 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
46
_____ cuffs are inaccurate and should not be used.
Finger cuffs
47
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
48
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
49
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
50
Patients with office BP above _____mm Hg do not need further confirmation of hypertension and should be treated.
160/100 mm Hg
51
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
52
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
53
_____ 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
54
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%
55
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
56
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
57
The evaluation of _____ activity has been proposed as an empiric method for the evaluation and treatment of hypertension
Plasma renin activity
58
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
59
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
60
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
61
The most common cause of secondary hypertension is _____, accounting for approximately 20% to 25% of all secondary hypertension cases.
Primary hyperaldosteronism
62
_____ 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
63
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).
64
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
65
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%).
66
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
67
Screening for primary hyperaldosteronism is most efficiently performed in potassium-repleted patients, using the ______.
Ratio of plasma aldosterone concentration to plasma renin activity (ARR)
68
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
69
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
70
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
71
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
72
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
73
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
74
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)
75
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
76
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
77
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
78
The nonsurgical option for patients with idiopathic hyperaldosteronism is the aldosterone antagonist _____, which has significantly better efficacy than its successor, eplerenone.
Spironolactone
79
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)
80
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
81
_____ is the “gold standard” test for OSA diagnosis but requires overnight evaluation and is expensive.
Polysomnography
82
A pheochromocytoma is a rare catecholamine-secreting tumor that arises from the _____ cells of the adrenal medulla.
Chromaffin cells
83
Approximately 90% of pheochromocytomas arise in the ______, 10% of patients have > ____ tumor, and 10% are ______.
90% adrenal gland
10% > 1 tumor
10% malignant
84
A pheochromocytoma may cause a nonischemic cardiomyopathy secondary to the impact of the _____ on the heart.
Catecholamines
85
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%
86
Approximately ___% of patients with neurofibromatosis type 1 (autosomal dominant von Recklinghausen disease: neurofibromas, with café au lait spots, axillary and/or ingui- nal freckling, hamartomas of the iris—Lisch nodules, bony abnormal- ities, central nervous system gliomas, and sometimes macrocephaly, or cognitive deficits, mediated by the NF1 tumor-suppressor gene on chromosome 17q11.2) will develop a catecholamine-secreting tumor, usually an adrenal pheochromocytoma.
2%
87
A **pheochromocytoma** is suspected if there is a _____ above the upper limit of normal of a **24-hour urine collection** of **catecholamines and metanephrines** or a significant elevation in plasma metanephrines.
Twofold or greater elevation
88
The sensitivity of plasma catecholamines for making the diagnosis of a pheochromocytoma is _____as a screening test.
Poor and not recommended
89
The specificity of plasma metanephrines, however, may be _____, and most patients with elevated metanephrines will not be found to have a pheochromocytoma
Poor
90
Certain drugs may cause an elevation in catecholamines and metanephrines including _____.
Withdrawal of these agents before diagnostic evaluation is usually needed to make a biochemical diagnosis of a pheochromocytoma.
Withdrawal from clonidine
TCA
Certain decongestants
Levodopa
Buspirone
Other psychoactive agents
91
Once a biochemical diagnosis of a pheochromocytoma is established, imaging studies are needed to localize the tumor. Because nearly 90% of the tumors arise from the adrenal gland, an _____ is recommended as an initial imaging test.
Abdominal CT or MRI
92
_____ may have some advantage over CT because T2-weighted images may be able to distinguish a **more hyperintense pheochromocytoma** from a benign adenoma.
MRI
93
_____ scintigraphy can be performed to detect extra-adrenal tumors or multiple tumors. MIBG resembles norepinephrine and is taken up by adrenergic tissue (including normal adrenal tissue).
Prior to performing this scan, certain antihypertensive medications should be discontinued if possible for at least 7-10 days before the test. These classes include:
Metaiodobenzylguanidine (MIBG) scintigraphy
HOLD 7-10 days before test:
CCB
Alpha/beta blockers (i.e., labetalol)
Many other non–BP-lowering agents
94
Pheochromocytomas need to be surgically removed to adequately treat the labile BP and because of their malignant potential. Removal of a pheochromocytoma can be difficult because of the **potential of causing a hypertensive crisis when the tumor is surgically manipulated**.
Adequate alpha- and beta-adrenergic blockade is required before surgical removal. _____ blockade is essential before _____ blockade to reduce the risk for a hypertensive crisis.
The irreversible long-acting alpha blocker______ is started 7 to 10 days prior to surgery at 10 mg once or twice daily and increased as needed to control the BP and prevent sudden spikes in BP.
Beta blockade, for example with metoprolol, is begun after adequate alpha blockade is achieved. Most pheochromocytomas can be removed laparoscopically.
Alpha blockade before beta blockade
Phenoxybenzamine 10mg OD or BID x 7-10 days before surgery
95
The pathophysiology of hypertension in Cushing syndrome overlaps somewhat with mineralocorticoid excess states, because excess cortisol often overwhelms the capacity of 11à-hydroxysteroid dehydrogenase type 2 to selectively degrade cortisol to cortisone in the aldosterone-producing cells of the adrenal cortex and can increase circulating levels of _____,which has only **mineralocorticoid activity.**
Deoxycorticosterone
96
The full-blown Cushing syndrome of hypertension, dyslipidemia, truncal obesity with striae, diabetes, hirsutism, acne, hyperglycemia, hypokalemia, and muscular weakness is less common today than in Cushing’s era. After an appropriate screening test (_____) has positive results, an endocrine referral for a second test is recommended before imaging studies are ordered.
Urinary-free cortisol
Late-night salivary cortisol
Overnight dexamethasone suppression test
97
In the majority of cases of Cushing Syndrome, dynamic testing of the hypothalamic-pituitary-adrenal axis is performed next, with either a:
(1) Corticotropin-releasing hormone test (which assays plasma cortisol and corticotropin levels before and after intravenous releasing hormone)
OR
(2) High-dose dexamethasone (2 mg every 6 hours) suppression test (which assays serum cortisol level)
98
Many patients with hyperthyroidism have wide pulse pressures (and therefore elevated SBP levels) and high pulse rates, but this is seldom missed, especially in younger patients. The ultrasensitive serum _____ level is widely available and most commonly used for screening.
TSH
99
After the diagnosis of hyperthyroidism, a nonselective beta blocker such as _____ may be specifically useful because it treats the tachycardia and hypertension and may inhibit peripheral conversion of thyroxine to triiodothyronine.
Propranolol
100
The role of hypothyroidism as a potential cause of hypertension (especially isolated diastolic) is less clear.The hypertension in hypothyroidism is predominantly _____ and usually less than 99 mm Hg.
Diastolic
101
Hypertension occurs in more than ___% of patients with excessive growth hormone release causing acromegaly, and it can be exacerbated by concomitant sleep apnea.
40%
102
The vast majority (98%) of cases of acromegaly are caused by a pituitary adenoma; serum _____ is the most useful initial laboratory screening test, although other tests (including the response of plasma growth hormone levels to an oral 75-g glucose load and prolactin levels) are often performed.
Insulin-like growth factor-1
103
Although generally not considered in most discussions of secondary (or remediable) hypertension, BP can be influenced b:
(1) Prescription or nonprescription medications or both
(2) Excessive dietary sodium intake
(3) Body weight/obesity
(4) Excessive alcohol intake
104
Modification of these factors is the cornerstone of therapy for primary hypertension and can mimic secondary hypertension. Of these factors, the most common issues relate to:
Excessive sodium intake
Poor sleep hygiene (i.e., getting less than 6 hours of uninterrupted sleep a night)
Excessive caffeine or other stimulants
Use of NSAIDs
105
Stopping the _____ can cure the hypertension after several weeks to months in most, but not all, women
OCP
106
NSAIDs result in a modest average hypertensive effect (up to approximately _____ mm Hg), but some patients can have larger, clinically significant BP elevation. **NSAID-induced hypertension** may also present as loss of BP control in patients taking a diuretic or a blocker of the renin-angiotensin system, whereas _____ tend to be less affected in NSAID users.
5 mm Hg
CCB
107
Alcohol has an **acute hypotensive** effect, but chronic use in large amounts (>_____drink-equivalents per day) is associated with increased BP.
>4-5 drink -equivalents/d
108
Glucocorticoids and mineralocorticoids can produce a dose-dependent rise in BP. Glucocorticoids with low mineralocorticoid activity like _____ induce lesser pressor responses.
Dexamethasone
Budesonide
109
Angiogenesis inhibitors, such as _____ can produce hypertension that often persists despite discontinuation. Because hypertension during the use of these drugs correlates with better oncologic outcomes (likely a reflection of successful antiangiogenic effect), treatment is usually continued unless reasonable BP control is not achievable or if severe kidney injury develops.
**Anti-VEGF antibodies** (bevacizumab, ramucirumab)
**Tyrosine kinase inhibitors** (sorafenib,sunitinib)
110
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
111
Poor sleep quality, if chronic, can cause paroxysmal hypertension and consistently elevated BP, especially during the _____
Afternoon and evening hours
112
Poor sleep quality (i.e., getting fewer than _____ hours of sleep nightly over a period of weeks) can lead to increase BP and increased BP variability. Moreover, data from the Nurses’ Health study show increases of 60% to 70% over 10 years in mortality in people with this problem
<6hrs
113
The mechanism of poor sleep quality contributing to elevated BP and paroxysmal bouts of very high BP relates to activation of both the sympathetic and RAAS. Sympathetic activity is also increased in _____.
Sleep deprivation
Restless leg syndrome
OSA
114
Patients without OSA who suffer from sleep deprivation, defined as less than a minimum of 6 hours of uninterrupted sleep, also have increased sympathetic activity. In this case, it is a consequence of reduced time in ______ or slow wave sleep that also affects the nocturnal dip in BP.
Non–rapid eye movement (NREM)
115
In contrast to reduced sleep time and quality,the increase in sympathetic activity associated with OSA is a function of _____ as the acute rise in BP parallels the severity of oxygen desaturation at night.
Intermittent hypoxia
116
It is also important to note that OSA-associated hypertension is only slightly reduced by _____treatment.
Continuous positive airway pressure (CPAP)
117
Hypertension can be both a cause and a consequence of CKD (i.e., estimated GFR [eGFR] _____ mL/min/1.73 m2)
<60 mL/min/1.73m2
118
In 2020, after diabetes, _____ remains the second most common cause of kidney failure worldwide resulting in renal replacement therapy
Poorly controlled hypertension
119
CKD is currently diagnosed and staged using the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) criteria from the National Kidney Foundation:
Persistent (3 months) evidence of kidney damage (e.g., proteinuria, abnormal urinary sediment, abnormal blood or urine chemistry levels, imaging studies, or biopsy)
120
Renally excreted beta blockers (e.g., atenolol, metoprolol, bisoprolol, nadolol, and acebutolol), and all ACE inhibitors, except _____, are reduced in dose or dosing frequency, but no serious adverse effects (other than possibly hyperkalemia) have been reported, if no adjustment of dosing is performed.
Fosinopril and Trandolapril
121
Also note that _____, normally twice-daily agents from the angiotensin receptor blocker (ARB) class when kidney function is normal,should be dosed once daily among those with an eGFR less than 60 mL/min/1.73 m2.
Losartan and Valsartan
122
Renovascular hypertension is most commonly due to _____.
Atherosclerotic disease
123
In the renal arteries, fibromuscular lesions tend to involve the _____ renal arteries and can lead to severe stenosis and aneurysms. In contrast, atherosclerotic renal artery disease more commonly involves the proximal portion of the renal arteries.
FMD: Mid or distal
Atherosclerotic: Proximal
124
Resistant hypertension defined as BP above target despite optimal treatment with _____.
3 antihypertensive agents with one of the medications being a thiazide diuretic
125
A greater-than-expected reduction in renal function with an ACEI or an ARB suggests the presence of _____.
Hemodynamically significant bilateral renal artery stenosis
126
Renal artery stenosis, by decreasing perfusion to the kidneys, tends to cause _____ of the RAAS.In some patients, treatment with a RAAS blocker can cause a marked worsening of renal function, suggesting dependence of kidney perfusion on renin.
Overstimulation
127
Medications that block the **RAAS are agents of first choice to treat renovascular hypertension** due to overactivation of this hormonal system.
Serum creatinine will usually increase with the introduction of an ACEI or ARB, although the increase is generally less than _____% from baseline.
A **significantly greater increase** in creatinine suggests **hemodynamically significant bilateral renal artery stenosis**
<30% from baseline
128
In individuals with significant bilateral disease, _____ can effectively increase renal perfusion, reduce BP or the number of antihypertensive medications, and preserve renal function.
Balloon angioplasty and stenting
129
Balloon angioplasty and stenting is usually the treatment of choice for fibromuscular dysplasia of the renal arteries because this disease is frequently _____
Bilateral
130
In patients with fibromuscular disease, predictors of success of angioplasty include:
* Age **< 40 years** at diagnosis
* Hypertension duration of **< 5 yrs**
* SBP **< 160 mm Hg**
131
Angioplasty and stenting are not recommended for unilateral renal artery stenosis because _____ with respect to clinical events was seen when angioplasty was added to optimal medical therapy using a RAAS blocker in patients with atherosclerotic renal artery disease.
No outcome advantage
132
A coarctation of the aorta is a narrowing of the descending aorta typically located just _____ at the insertion of the ductus arteriosus
Distal to the left subclavian artery
133
Although most discrete constrictions of the aorta occur in or near the ductus arteriosus, there is growing awareness that this fifth-most common form of congenital CV disorders constitutes a spectrum of aortic and vasculopathic disorders and is _____by surgical procedures that relieve the obstruction
Not always “cured”
134
Many cases of CoA are identified by suggestive physical findings (e.g., murmur, BP lower in the legs than the arms, radial-femoral pulse delay), some after imaging studies done for other reasons (e.g., _____), and others during investigation of associated abnormalities (e.g.,bicuspid aortic valve).
Rib notching or a “3” sign on chest radiograph, the latter of which results from indentation of the aorta, with prestenotic and poststenotic dilation
135
Most patients of CoA can be treated with _____; this can be followed by definitive surgical correction later, if needed
Percutaneous catheter balloon dilation with aortic stent placement
136
Unfortunately, 25% to 68% of patients with a coarctation have persistent hypertension despite satisfactory procedure results, with _____ being strong predictors of persistent hypertension
* Age at the time of surgery
* Age at follow-up
* Type of intervention
137
Antihypertensive therapy should be started when:
(1) **Confirmed diagnosis** of hypertension, meaning **> 2 separate readings** at separate times with BP levels consistently **> 130/80 mm Hg**
(2) **Dietary and lifestyle intervention** has been tried for a brief period. If BP is **> 20/10 mm Hg** above the goal, then both lifestyle and antihypertensive therapy should be started concomitantly.
138
Meta-analyses of all commonly used antihypertensive drug classes demonstrate that, regardless of the agent used, reduction in BP corresponds to reduction in CV events if BP reduction is achieved. This reduction in CV risk, however, is predominantly seen in people with stage _____ hypertension (>140/90 mm Hg) with much less outcome data to support risk reduction in stage 1 hypertension (systolic >130 to 139 mm Hg or diastolic 80 to 89 mm Hg).
Stage 2 hypertension
139
Events that drive CV risk reduction are derived predominantly from reduced incidence of:
Stroke
MI
HF
140
In all trials to date the group with the best overall BP control has the best outcomes. An exception to this generalization is _____, a CV outcome trial in over 11,000 people.194 In this trial, both groups had similar BP control, and both were randomized to the same ACEI (benazepril), yet the group initially randomized to a single-pill combination of benazepril with a calcium antagonist had a 20% CV risk reduction compared with the ACEI plus diuretic group. The observed benefit for the benazepril-amlodipine combination also extended to slowing CKD progression.
Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH)
ACEi + CCB (Benazepril + Amlodipine)
141
All guidelines regardless of origin place emphasis on ______. Many studies document the effects of both sodium and potassium intake on BP
Lifestyle modifications with emphasis on sodium restriction
141
In the _____trial, the combination of weight loss and sodium restriction showed a drop of 5.3 ± 1.2 mm Hg in the SBP and 3.4 ± 0.8 mm Hg DBP in obese, older patients with hypertension.The goal of sodium restriction was 1.8 g/24 hr, and the goal for weight reduction was 10 lb.
Trial of Nonpharmacologic Interventions in the Elderly (TONE)
142
Intake of NSAIDs should be decreased to a minimum, because older patients are more likely to take NSAIDs for arthritis and pain. These drugs are known to cause elevations in BP by inhibiting the production of vasodilatory prostaglandins and may increase BP by as much as _____ mm Hg.
6 mm Hg
142
NSAIDs’ BP-raising effects can be blunted by both _____ and, to less extent,diuretics.
CCB
Diuretics
143
ACEI and ARBs are effective adjuncts but because of the _____ renin status in **older people** they are not as successful in lowering BP.This is also true for **younger African Americans** patients.
Lower
144
______, are recommended for initiating therapy in the older patient
**Thiazide diuretics** such as hydrochlorothiazide, chlorthalidone, indapamide, and bendrofluazide, as well as **calcium antagonists**
145
Nonpharmacologic intervention with highest BP lowering effect
DASH -11mm Hg
146
Diuretics cause an initial reduction of _____ in more than 50% of patients and are well tolerated and inexpensive. However, they can cause hypokalemia, hypomagnesemia, and hyponatremia and are therefore not recommended in patients with baseline electrolyte abnormalities or those with a history of hyponatremia. Serum potassium level should be monitored, and supplementation should be given if needed.
Intravascular volume,
Peripheral vascular resistance
BP
147
Compared the safety and efficacy of intensive lowering of systolic blood pressure (SBP) to <120 mm Hg versus routine management to <140 mm Hg
Patients were randomized to intensive SBP lowering (target <120 mm Hg) or routine SBP management (target <140 mm Hg).
The primary outcome, myocardial infarction (MI), acute coronary syndrome (ACS), stroke, congestive heart failure (CHF), or cardiovascular (CV) death, was significantly lowered in the intensive BP management arm compared with the routine management arm (5.2% vs. 6.8%, hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.64–0.89; p < 0.0001).
SPRINT (Systolic Blood Pressure Intervention Trial)
the older group of patients randomized to a lower level of BP less than 120 mm Hg did well and in many cases better than those at BPs targeted to less than 140 mm Hg, leading to the assertion that older patients should be treated to lower levels of BP.
148
Calcium antagonists are well suited for older patients whose hypertensive profile is based on **increasing arterial dysfunction secondary to decreased atrial and ventricular compliance**; **dilates coronary and peripheral arteries** in doses that do not severely affect myocardial contractility
Most adverse effects relate to vasodilation, causing ankle edema, headache, or postural hypotension.
Ankle edema is **not secondary to sodium retention**, because calcium antagonists are **natriuretic when given initially**, but the _____ in older people is the major contributor
Profound vasodilation with poor venous return
149
First- generation immediate-release drugs, such as _____, should be avoided in patients with **left ventricular dysfunction**. Non-DHPs can precipitate **heart blocks** in older adults with underlying conduction defects.
Nifedipine
Verapamil
Diltiazem
150
Theoretically, as aging occurs, there is a reduction in angiotensin levels; thus, _____ may not be as effective in older adults.
ACEis
151
The use of ACEIs is beneficial in the reduction of morbidity and mortality in patients with myocardial infarction, reduced systolic function, heart failure, and reduction in the progression of diabetic renal disease and hypertensive nephrosclerosis.
It must be noted that individuals older than 70 years of age tend to drink small amounts of fluid, and hence this makes them more vulnerable to decline in kidney function by RAAS blockade.Thus it is recommended that elderly patients _____ to prevent volume depletion.
Increase their fluid intake
RAAS blockers may provide greater benefit for CV and renal risk reduction than diuretics, based on data from the ACCOMPLISH trial.
152
Beta blockers have established roles in patients with hypertension complicated by certain arrhythmias, migraine headaches, senile tremors, coronary artery disease, or heart failure.
_____, a selective beta1 blocker with NO properties, does not show associated symptoms of depression, sexual dysfunction, dyslipidemia, and hyperglycemia in older adults, unlike earlier generations of beta blockers.
Nebivolol
153
Potassium-sparing diuretics are useful when combined with other agents only in people with an eGFR greater than ____ mL/min otherwise the rise of hyperkalemia is increased. Aldosterone-blocking agents like spironolactone and eplerenone reduce vascular stiffness and SBP
They are very helpful for patients with hypertension with heart failure or primary hyperaldosteronism. ___________ and ___________ are the limiting adverse reactions that may occur in men using spironolactone but are less frequent with eplerenone.
>45 mL/min
Gynecomastia and sexual dysfunction
154
The _____ are most useful when combined with another diuretic.
Epithelial sodium transport antagonists (amiloride,triamterene)
155
The strongest level of evidence to support slowing of CKD progression argues for BP levels below _____ mm Hg and the use of RAAS-blocking agents in people with stage 3 or higher CKD who have very high albuminuria
<140/90 mm Hg
156
The ____ Trial included a cohort of patients with nondiabetic kidney disease but failed to reach a convincing endpoint of slowing CKD progression. Nevertheless, guidelines were put out arguing for a BP goal of less than 120/80 mm Hg for everyone with CKD. Unfortunately, this is not supported by the totality of the data and hence, the prior guidelines that recommended the BP goal of **130/80 mm Hg** should be adhered to despite no further renal benefit, although there is CV risk reduction at this level.
SPRINT
The ACC/AHA BP guidelines focus on CV risk reduction rather than a focus on renal preservation, because the BP range of 125 to 130 mm Hg has not been shown to harm the kidneys yet can further reduce CV events.2
157
A review of clinical trials where hyperkalemia developed when managing hypertension in CKD found three risk predictors:
(1) eGFR of less than 45 mL/min/1.73 m2,
(2) serum potassium level above 4.5 mEq/L, and
(3) body mass index of <25
158
Further, critically important nuances in BP management in CKD patients are:
Sodium restriction to less than 2400 mg/day
-failure to reduce sodium intake suppresses the RAAS system and hence reduces efficacy of RAAS blockers.Thus failure to reduce sodium intake is a cause of resistant hypertension
Reduced alcohol consumption
Aerobic but not isometric exercise
159
The_____ trial is a seminal trial to evaluate level of glycemic control and BP control on CV outcomes in people with diabetes. The results of the BP arm of this trial failed to show a reduction in major CV events from more aggressive BP control.
Action to Control Cardiovascular Risk in Diabetes (ACCORD)
160
The _____ like ACCORD did not show a benefit from the lower BP group, which aver- aged well above 140/90 mm Hg. Additional findings from post hoc analyses of diabetes subgroups of other trials also failed to show CV outcome benefit of BP levels below 130/80 mm Hg
United Kingdom Prospective Diabetes Study (UKPDS)
Additional:
RAAD blockers does not possess any specific advantages over other antihypertensive classes in people with diabetes who do not have nephropathy or albuminuria with levels at or above 300 mg/day
No evidence that RAAS blockers benefit people with normotension with or without microalbuminuria from developing declines in kidney function
161
Elevations in BP in dialysis patients are almost exclusively due to _____. Hypertension control related directly to volume management is a more common problem in hemodialysis than in peritoneal dialysis.
Excessive volume
162
It appears that _____therapy is superior to RAAS blockade in patients undergoing hemodialysis to reduce CV morbidity and all-cause hospitalizations.
Beta-blocker
163
_____ is the prominent mechanism of hypertension in dialysis patients, but other pathways, such as arterial stiffness, activation of the RAAS and SNSs, endothelial dysfunction, sleep apnea, and the use of erythropoietin-stimulating agents may also be involved.
Sodium and volume excess
If BP remains elevated after appropriate treatment of sodiumvolume excess, the use of antihypertensive agents is necessary.
164
Although there is no generalizable approach to manage BP in dialysis, the following points are vital to have an accurate assessment of BP:
(1) the most representative BP is the one taken the morning after dialysis, and
(2) there should be a minimum of two and ideally three readings obtained 1 to 2 minutes apart during those morning readings and then averaged.
165
Given that _____ are the most common causes of death in dialysis patients, **beta blockers** have an important role in the BP-lowering armamentarium, unlike the general population
HF
SCD
166
Of all potential strategies that might reduce the incidence of heart failure in CKD, none appears to have higher yield than the treatment of _____.
Hypertension
HFpEF - The best guidance continues to prompt a unique focus on concomitant comorbidities, including hypertension, for which evidence-based clinical practice guidelines exist.
HFrEF - ACEI, ARBs, evidence-based beta-blockers, mineralocorticoid receptor antagonists, hydralazine and isosorbide dinitrate (ISDN), and implantable cardioverter-defibrillator/cardiac resynchronization therapy (ICD/CRT); and newer therapies: valsartan/sacubitril and ivabradine
167
The _____ trial was one of the first hypertension trials to include a prespecified endpoint examining the efficacy of antihypertensive therapy (chlorthalidone 12.5 to 25 mg plus atenolol 25 to 50 mg, if needed) in the prevention of heart failure. Participants randomized to diuretic- based stepped care had a 49% reduction in fatal and nonfatal heart failure events during an average follow-up of 4.5 years.
Systolic Hypertension in Elderly Program (SHEP) Trial
Chlorthalidone + Atenolol
168
In the _____ Trial, patients randomized to the indapamide plus perindopril (as needed to achieve a target BP of 150/80 mm Hg) group achieved a 64% reduction in heart failure events compared with placebo at 2 years.
Hypertension in the Very Elderly Trial (HYVET)
Indapamide + Perindopril
169
Trials such as the _____ study demonstrated that ACEIs could also reduce heart failure events in high-risk participants. In this study, among participants with diabetes mellitus or established vascular disease, ramipril treatment was associated with a 23% reduction in heart failure events after a mean of 4.5 years of follow-up.
Heart Outcomes Prevention Evaluation (HOPE)
Ramipril
170
In a recent high-quality meta-analysis of 123 BP-lowering trials, including 613,815 total participants, meta-regression demonstrated that for every 10–mm Hg reduction in SBP the risk of heart failure was reduced by ____%
Every 10 mmHg = 27% HF risk reduction
However, in this meta-analysis as well, investigators noted the greater efficacy of thiazide diuretics and inferiority of CCBs for heart failure prevention.
Hypertension treatment and control with **thiazide diuretics plus ACEIs or ARBs** are essential parts of a heart failure prevention strategy.
171
The role of ARBs in HFpEF has been studied in the _____. Both trials failed to meet their primary outcome that included composite endpoints consisting of all-cause mortality, CV death, heart failure hospitalization, and/or hospitalization for a CV cause
Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM)-Preserved
Irbesartan in Heart Failure with Preserved Ejection Fraction Study (I-PRESERVE).
172
The _____ study and the Aldosterone Receptor Blockade in Diastolic Heart Failure (Aldo-DHF) both tested the effects of mineralocorticoid receptor antagonists in patients with HFpEF.264,265 Both trials demonstrated improvements in diastolic func- tion in patients treated with mineralocorticoid receptor antagonists, but this did not translate to improvements in exercise capacity
Randomized Aldosterone Antagonism in Heart Failure with Preserved Ejection Fraction (RAAM-PEF)
173
The _____ was the largest trial to test the effects of mineralocorticoid receptor antagonists in patients with HFpEF.266 After a mean follow-up of 3.3 years, spironolactone did not reduce the pri- mary outcome of composite CV events,but it did reduce heart failure hospitalizations by 17%.
Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT)
Spironolactone - HF hospitalizations
174
These findings are even more relevant in the context of the SPRINT, in which participants at high risk for CV disease (e.g., 10-year cardio- vascular disease [CVD] risk 15%, age 75 years, CKD or established vascular disease) were randomized to standard BP lowering (target SBP <140 mm Hg) versus intensive BP lowering (target SBP <120 mm Hg).269 After a median follow-up of 3.3 years, intensive treatment was associated with a 25% reduction in major CV events, inclusive of heart failure, compared with standard treatment. However, the beneficial effect was primarily driven by a __% reduction in heart failure and a __% reduction in CV death. These studies establish the imperative to treat BP intensively in high-risk individuals to prevent heart failure.
HF: 38%
CV death: 43%
175
Define Resistant Hypertension _______
Studies also show that patients with resistant hyperten- sion who are ______ have an increased risk for CV events compared with patients with nonresistant hypertension
Failure to achieve a goal BP of less than 140/90 mm Hg in patients who are adherent with maximal tolerated doses of three antihypertensive drugs, one of which must be a diuretic appropriate for kidney function
> 55 years
Black ethnicity
High BMI
Diabetes
CKD
176
Common causes of resistant hypertension include:
(1) nonadherence with medication
(2) volume overload secondary to poor kidney function
(3) nonadherence with a low-sodium diet
177
The renal nerves enter the kidney at the hilum and branch out into segmental arteries throughout the kidney. They contain sympathetic efferent and sensory afferent fibers and are recognized as important controllers of kidney function and BP. Additionally, sympathetic efferent fibers innervate the renal arteries, arterioles, renin-secreting juxtaglomerular cells, veins, and most tubular segments. Stimulation of renal sympathetic nerves increases _____ depending on stimulation frequency.
Increase renal vascular resistance, tubular reabsorption of NaCl, and renin release
178
Two initial clinical studies evaluated RDN in a multicenter study that enrolled 45 patients with SBP greater than 160 mm Hg on three or more antihypertensive drugs including a diuretic but did not include a sham control. Reductions in office SBP/DBP after RDN were impressive, averaging −22/−11 and −27/−17 mm Hg after 6 and 12 months, respectively. In 10 patients, renal norepinephrine spillover, measured using an isotope dilution method, was reduced by an average of 47%, demonstrating that the RDN procedure was moderately effective in ablating the renal nerves. In a more recent study, doing a proper denervation involving branched nerves within the kidney reduced norepinephrine by __%
92%
179
These data generated the first definitive randomized, sham- controlled trial, ______. A total of 533 patients with resistant hypertension taking at least three different BP medications were randomly assigned in a 2:1 ratio to undergo denervation or a sham procedure.The average decreases in SBP at 6 months were −14.1 and −11.7 mm Hg in RDN and sham groups, respectively, with no significant differences in 24-hour ambulatory SBP.After 12 months, the reductions in office BP were similar in the RDN and sham groups
SYMPLICITY HTN-3
180
The main reasons for the poor outcome after RDN revolved around:
Procedural adequacy of denervation and location of denervation
181
Learning from all the mistaken assumptions and other trial issues as well as discussions with the FDA, a new catheter was invented (SPYRAL), and the _____ trials ensued. These prospective, randomized, double- blind, sham-controlled studies were designed to assess the impact of RDN in patients with uncontrolled BP and who were medication naive or had discontinued medication and in patients being treated with one to three commonly prescribed antihypertensive medications. Both studies used a new multielectrode catheter designed to permit reliable circumferential four-quadrant renal nerve ablation. Also, RDN was performed in the main renal arteries and branches, an approach that likely produces more complete renal nerve ablation. Both studies showed significant reductions in BP through 3 months, compared with sham controls, with no major adverse events.The primary results from the SPYRAL HTN-OFF MED trial confirmed earlier results demonstrating a clear 6.6/4.4–mm Hg reduction in office systolic pressure. In contrast to SYMPLICITY HTN-3 in which participants received an aver- age of greater than 5 antihypertensive agents, the effect of the sham procedure was negligible with changes in ambulatory SBP/DBP from baseline of only −0.5/−0.4 mm Hg.271
SPYRAL HTN-OFF MED and SPYRAL HTN-ON MED Trials
182
The _____ evaluated 45 patients with resistant hypertension, SBP 160/ DBP 90 mm Hg. Medications were kept constant before and over the 3 months of the trial, but medication adherence was not critically assessed. At each visit, the device was temporarily turned off to assess BP without activation. At that time, BP increased rapidly toward baseline levels, confirming the sustained antihypertensive effects of baroreceptor-activation(BA) therapy, and demonstrating the rapid off transient response to deactivation.
DEBuT-HT European trial (Device Based Therapy in Hypertension Trial)
Baroreceptor-activation(BA) therapy
183
In the _____ Trial, subjects were implanted with the Rheos system, and 265 patients were randomized 2:1 1 month after surgery to receive BA the first 6 months (immediate BA) or to delay BA for the first 6 months of the trial (delayed BA). For the immediate BA group, SBP was reduced by 16 mm Hg at 6 months and 27 mm Hg at 12 months when compared with the 1-month postimplant values before activation. For the delayed BA group, reductions in SBP were 9 and 25 mm Hg at 6 and 12 months,r espectively.The trial was successful in meeting the prespecified sustained 12-month efficacy endpoint; however, the acute 6-month primary efficacy endpoint was missed. The failure to meet the prespecified acute efficacy endpoint was apparently due primarily to a larger and more variable reduction than expected in SBP at 6 months in the group with the inactive implants and likely reflected the less-than-optimal trial design. Beyond efficacy considerations, the prespecified endpoint for procedural safety was not met, with 9% of patients developing transient or permanent nerve injury and 5% having general surgical complications.
Rheos Pivotal Trial
184
The _____ trial was a single-arm, open-label study that evaluated efficacy and safety of the second-generation system for BA in 30 patients with resistant hypertension. The implant procedure was minimally invasive and required only unilateral suturing of a miniaturized electrode on to the surface of the carotid sinus. The primary efficacy objective of this trial was to describe reductions in office BP through 6 months of BA. Compared with the Rheos-HT trial ,the number of patients who suffered from procedural complications decreased from 25% to 3%. Of particular interest, 6 of the 30 patients enrolled in this trial underwent previous RDN, which was unsuccessful in lowering BP.After 6 months of BA, reductions in SBP and HR were comparable in these patients when compared with the subjects with intact renal innervation.
Barostim Neo Trial
185
An alternate approach for chronically activating the carotid baroreflex is being evaluated in clinical trials. Rather than increasing baroreceptor afferent activity by electrically stimulating the carotid sinus, the concept behind the _____ is amplification of the signal sensed by carotid baroreceptors during distortion of their nerve endings by vascular stretch during systole. Signal amplification is achieved by a passive, flexible, self-expanding endovascular implant that reshapes the carotid sinus during systole, increasing the radius while preserving pulsatility. In so doing, this increases wall strain and, thus, baroreceptor activation during spontaneous changes in systolic pressure.
MobiusHD system (Vascular Dynamics,Inc)
186
A _____ is the combination of elevated BP levels (with no specific diagnostic BP level) and signs or symptoms of acute, ongoing target-organ damage
Hypertensive emergency
187
Traditionally, patients who presented with significantly elevated BP levels usually above an SBP of 180 mm Hg, but no acute, ongoing target-organ damage, were diagnosed with a “_____”
Hypertensive urgency
188
The initial evaluation of a severely hypertensive patient includes:
(1) Thorough inspection of the optic fundi (looking for acute hemorrhages, exudates, or papilledema);
(2) Mental status assessment;
(3) Careful cardiac, pulmonary, and neurologic examination;
(4) Quick search for clues that might indicate secondary hypertension (e.g., abdominal bruit, striae, radial-femoral delay);
(5) Laboratory studies to assess renal function (dipstick and microscopic urinalysis, determination of serum creatinine level).
189
Several options for intravenous drug treatment exist for hypertensive emergencies, but _____ is the least expensive and most widely available.It must be kept in the dark and is metabolized to cyanide and/or thiocyanate, particularly during long-term infusions.
Nitroprusside
190
_____, a dopamine-1 agonist, is very effective and acutely improves several parameters of renal function in the treatment of hypertensive emergencies
Fenoldopam mesylate
191
_____ is a DHP calcium antagonist that is hydrolyzed within minutes by ubiquitous serum esterases; it is administered in an emulsion containing soy and egg proteins (either of which can cause immunologic reactions in allergic patients). Its elimination is not importantly affected by hepatic or renal functional impairment.
Clevidipine
192
Clevidipine and its older, longer-acting cousin, nicardipine, are often used for patients with _____ ,because the reflex tachycardia is usually offset by coronary vasodilation.
CAD
193
In the treatment of hypertensive emergencies, _____ is typically used only for subarachnoid hemorrhage.
Labetalol can be given as an intravenous infusion and easily converted to an ongoing oral dose.
Nimodipine - SAH
194
The quickest therapeutic response to a hypertensive emergency is recommended for an ___________
In this condition the BP should be lowered within ___ minutes to an SBP below ____ mm Hg (neither of which is supported by a strong evidence base), typically with a beta blocker (to reduce shear stress on the dissection) and a vasodilator.
Acute aortic dissection
BP should be lowered within 20 mins to SBP < 120 mm Hg
With a BB and a vasodilator
195
Controversy exists about if, and when, BP lowering should be attempted in the setting of an acute ischemic stroke. If the patient is a candidate for acute thrombolytic therapy and the BP is higher than ____ mm Hg, acute BP lowering is recommended.
>180/110 mm Hg
196
All other types of hypertensive emergencies can be handled with a gradual lowering of BP (typically _____)
10% to 15% during the first hour and a further 10% to 20% during the next hour, for a total of approximately 25%
197
Patients who present with hypertensive crises involving cardiac ischemia/infarction or pulmonary edema can be managed with ______ although typically a combination of drugs (including an ACEI for heart failure or left ventricular dysfunction) is used in these settings. Efforts to preserve myocardium and open the obstructed coronary artery (by thrombolysis, angioplasty,or surgery) also are indicated.
NTG
Clevidipine
Nicardipine
Nitroprusside
198
Hypertensive emergency involving the kidney commonly is followed by a further deterioration in renal function even when BP is lowered properly. The most important predictor of the need for acute dialysis is not the BP level but instead the _____.
Degree of renal dysfunction (both eGFR and degree of albuminuria)
199
In patients with hypertensive emergency of the kidneys, some physicians prefer _____ to nicardipine or nitroprusside in this setting because of its lack of toxic metabolites and specific renal vasodilating effects.
The need for acute dialysis often is precipitated by BP reduction in patients with preexisting stage 3 to 5 CKD, but many patients are able to avoid dialysis (and a remarkable few even discontinue it) in the long term if BP is carefully and well controlled during follow-up
Fenoldopam
200
Hypertensive emergency resulting from catecholamine excess states (e.g., pheochromocytoma, monoamine oxidase inhibitor crisis, cocaine intoxication) are most appropriately managed with an _____.
IV alpha blocker (e.g., phentolamine), with a beta blocker added later, if needed
201
Many patients with severe hypertension caused by sudden withdrawal of antihypertensive agents (e.g., clonidine) are easily managed by _____
Giving one acute dose of the missed drug
202
Hypertensive emergency during pregnancy must be managed in a more careful and conservative manner because of the presence of the fetus. _____ are the drugs of choice, with _________ being drugs of second choice in the United States; __________ are contraindicated.
Delivery of the infant is often hastened by the obstetrician to assist in management of hypertension in pregnancy.
Magnesium sulfate, methyldopa, and hydralazine - DOC
Oral labetalol and nifedipine - second line
Contraindicated- Nitroprusside, ACEIs, and ARBs
203
The BP in many such patients with hypertensive urgency spontaneously falls during a 30-minute period of _____
Quiet rest
204
Conversely, immediate-release nifedipine capsules can cause _____
Precipitous hypotension
stroke
Myocardial infarction
Death
205
The most important aspect of managing a hypertensive urgency is to _____ where adherence to antihypertensive therapy during long-term follow-up will be more likely.
Refer the patient to a good source of ongoing care for hypertension,
206
In short, patients presenting with a hypertensive emergency should be diagnosed quickly and started promptly on effective parenteral therapy (often nitroprusside 0.5 μg/kg/min) in an intensive care unit. BP should be reduced by approximately ___%, gradually over 2 to 3 hours. Oral antihypertensive therapy should be instituted, usually after approximately ____ hours of parenteral therapy; evaluation for secondary causes of hypertension may be considered after transfer from the intensive care uni
IV - 25% over 2-3 hours
Start oral after 8-24 hours
207
Adrenocortical hormone synthesized in the zona glomerulosa, plays a critical role in hypertension through its effects on sodium reabsorption largely mediated by transcriptional effects, via activation of the mineralocorticoid receptor, leading to increased expression of the epithelial sodium channel (ENaC).
Aldosterone
Extensive nonepithelial effects include vascular smooth muscle cell proliferation, vascular extracellular matrix deposition, vascular remodeling and fibrosis, and increased oxidative stress leading to endothelial dysfunction and vasoconstriction.
208
________ 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
209
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
210
Effect of natriuretic peptides
Immediate BP lowering due to **systemic vasodilation and decreased plasma volume**, the latter caused by fluid shifts from the intravascular to the interstitial compartment
All natriuretic peptides directly increase GFR, which in volume-expanded states is mediated by an **increase in efferent arteriolar tone and increased filtration coefficient (Kf ).**
Natriuretic peptides also **inhibit renal sodium reabsorption** through both direct and indirect effects.
Direct effects include
- decreased activity of Na+ -ATPase and the sodium-glucose cotransporter in the proximal tubule
- inhibition of the ENaC in the distal nephron.
Indirect effects
-the inhibitory effects of natriuretic peptides on renin and aldosterone release
211
__________ is the most important to BP regulation of the endothelium
Nitric Oxide
