A 42-year-old Caucasian man is referred to you for evaluation of a blood pressure (BP) of 136/86 mmHg. He has no family history of hypertension (HTN) or heart disease. He does not smoke. His creatinine and glucose are normal. According the Seventh Joint National Committee (JNC 7), how would you classify his BP ?

According to JNC 7, HTN is classified into normal BP, prehypertension, stage 1 HTN, and stage 2. The following table shows the classification of BP, as proposed by JNC 7 (Table 6.1 ).

It is evident from the table that the above individual has prehypertension, and only lifestyle modification is needed to improve his BP to normal range. However, some argue for drug management because BP in the upper range, as in this individual, may progress to stage 1 HTN, and also carries risk for cardiovascular disease. Stage 3 HTN has been dropped from JNC 7. Thus, option B is correct.

A 44-year-old woman is sent to you for evaluation of her BP. During her first visit, the BP is 144/82 mmHg (similar BP on three measurements). She brings her home BP measurements, which range from 120–124/64–68 mmHg. Based on these BP values, which one of the following conditions she may have at this time?

White coat HTN is defined as daytime out-of-office BP <135/85 mmHg and an office BP >140/90 mmHg. This high office BP with normal home BP is found between 15 and 30 %, and most common in women and the elderly. It is usually a benign condition; however, lifestyle modification should be instituted. Pharmacotherapy is usually not indicated. Thus, option B is correct. Other forms of HTN are not applicable to this woman.

A 32-year-old man with family history of HTN measures his own BP daily and keeps in his diary. He visits his primary care physician, and his BP is found to be 124/72 mmHg, which is much lower than his home BP. He insists that his BP be measured 2 h later, which was found to be 125/73 mmHg. He asks you to clarify about this discrepancy between office and home BP measurements, and you would say that he has:

In the last 15 years, a new form of HTN has been recognized with the use of ambulatory BP or home BP measurements. This form of HTN is called masked HTN , which is defined as low office or clinic BP and high ambulatory or home BP. Masked HTN is present in about 10 % of general population, 20 % of elderly, and 14 % of untreated stage 1 hypertensive subjects. Unlike white coat hypertensives, subjects with masked HTN are at risk for cardiovascular morbidity. Also, masked hypertensive subjects are at higher risk for cardiovascular disease than normotensive subjects. Thus, screening for masked HTN is important by self-monitoring his or her BP regularly. Lifestyle modification or appropriate drug therapy may prevent long-term complications of HTN. Some subjects with masked HTN may develop prehypertension or sustained hypertension. Thus, the answer to your patient’s question is D. Other options are incorrect.

Which one of the following factors causes variability in BP measurement ?

Many factors either in the clinic or home affect BP values. BP is high in cold season because of vasoconstriction and low in summer season because of vasodilation. The BP varies during the daytime, and is usually high from 10 am to 6 pm compared to BP values at nighttime (low). Eating lowers BP because of splanchnic vasodilation, and this is particularly seen in the elderly. Smoking acutely elevates BP. Thus, option E is correct.

A 50-year-old woman is referred to you for evaluation of HTN, and you found that systolic BP in the right arm is 6 mmHg higher than the left arm. Her BP is 142/89 mmHg with a pulse rate of 72 beats/min. Femoral pulses are strong and present bilaterally. You repeated her BP 1 week later and found a similar difference in both arms. With regard to her inter-arm difference in BP and its management, which one of the following choices is CORRECT?

It is not uncommon to see a small difference in both systolic and diastolic BPs between the right and left arm. This difference is more pronounced in patients with HTN. Usually, the BP in the right arm is slightly higher than the left arm. The difference in systolic BP between the arms is usually 10 mmHg. Systolic BP difference >10 mmHg suggests PVD, and suggests a vascular assessment. In this patient, the inter-arm difference is only 6 mmHg, and does not warrant further evaluation. Thus, choice D is correct. Starting antihypertensive therapy is premature. It is recommended that the arm with higher BP should be used for further BP measurements in the clinic, office, or home. Coarctation of the aorta is characterized by hypertension with weak or absent femoral pulses usually in a young patient. The above patient is a middle-aged individual with strong femoral pulses bilaterally. Thus, choice C is incorrect.

A 72-year-old African American man with HTN is referred to you because of dizziness despite a BP of 150/102 mmHg. There are no sitting and standing BP changes, but a slight increase in pulse rate on standing is noticed. He is on long-acting diltiazem 180 mg daily, and not on any other medications. He has no retinopathy or proteinuria. CXR is normal. However, his brachial arteries feel hardened. Which one of the following is the MOST likely cause of his dizziness?

In elderly patients with documented high BP and without target organ damage, one needs to consider pseudohypertension as a cause of dizziness. Pseudohypertension occurs when a falsely elevated BP reading obtained with a BP cuff while an intraarterial catheter shows a normal BP. This elevated cuff BP is due to thickened or calcified brachial arteries that are not easily compressible with the BP cuff. This phenomenon of pseudohypertension came from Osler’s writing that he mistrusted the BP readings in patients with stiff arteries. The Osler’s maneuver is elicited when the cuff is inflated above the systolic BP and the brachial or radial pulses, which should be obliterated, are still palpable. When patients with pseudohypertension are treated with antihypertensive medication (s), they develop hypotensive symptoms despite high cuff BP. The above patient’s dizziness is compatible with pseudohypertension. Thus, option C is correct. In autonomic insufficiency, the pulse does not increase on standing. Changing to a diuretic will not improve his symptoms. Thus, options A and D are incorrect.

A 55-year-old man with type 2 diabetes and HTN is found to have nondipping of his BP during 11 pm to 4 am despite adequate BP control. Which one of the following complications is associated with nondipping ?

BP falls at night during sleep and also during inactivity. Although arbitrary, the nocturnal fall in both systolic and diastolic BP varies from 10 to 20 %. This condition is called dipping. When nocturnal BP falls <10 %, the condition is called nondipping. Studies have shown that nondipping is related to sympathetic overactivity. Nondipping is a risk factor for several conditions, including LVH, CVD, stroke, progression of proteinuria or albuminuria, and loss of renal function. Therefore, option E is correct. Studies have suggested that inhibitors of renin-AII-aldosterone system may cause dipping in nondippers, and improve the above associations of nondipping.

Home BP monitoring (HBPM ) by hypertensive patients is being encouraged by many primary care physicians. Which one of the following advantages does HBPM have over office BP measurement?

HBPM is becoming popular than office BP measurement for all of the above mentioned choices. In addition, HBPM is cost-effective (reduced cost). Several studies have reported lower BPs at home compared to either office or clinic BPs. One study reported average home BP of 123/78 mmHg compared to office BP of 130/82 mmHg. Thus, HBPM is better and lower than office or clinic BP recordings, making E as the correct choice.

Ambulatory BP monitoring ( ABPM ) is important in which one of the following conditions?

Accurate BP readings are necessary for diagnosis of HTN and for assessment of its therapy. In general, most of the patients have high office BP readings compared to either self-monitored (home) or 24-h BP readings. ABPM accomplishes all of the conditions mentioned from A to D. Recognition of dipping or nondipping and BP readings during sleep can be accurately obtained from ABPM. BP readings from ABPM can be used to assess the risk for target organ damage for appropriate antihypertensive therapy, and also for calculating pulse pressure. Thus, ABPM has several advantages over BP recordings taken in the office setting. Thus, option E is correct.

Regarding ambulatory BP monitoring ( ABPM ) in chronic kidney disease (CKD) patients, which one of the following statements is CORRECT?

In normal subjects, the BP drops (dipping) by 10-20 % during sleep period. This circadian rhythm is lost in CKD, resulting in higher prevalence of nondipping in CKD. A patient who shows high BP during sleep is referred to as riser. The prevalence of nondipping in CKD patients is much higher compared to non-CKD or essential hypertensive patients. Also, nondipping increases with increasing loss of renal function (i.e., decreasing eGFR). ABPM has a good predictive value of both renal and CV outcomes. The combination of both ABPM and eGFR has an additive effect in predicting renal and CV outcomes. Thus, option E is correct

Central aortic pressure (central BP) is found to be superior to brachial (peripheral) BP in which of the following conditions?

PWV is a measure of aortic stiffness, and it can be measured between the carotid and femoral arteries. Arterial stiffness causes faster PWV, whereas distensible arteries cause slow PWV. With each contraction of the left ventricle during systole, a pulse wave is generated which travels from the ascending aorta to the branching points of peripheral arteries. These peripheral arteries (arteries and arterioles) resist further propagation; therefore, the wave is reflected back to the heart. In normal arteries, the reflected wave merges with the forward traveling wave in diastole and augments coronary and cerebral perfusion. If arteries are stiff due to disease conditions such as atherosclerosis, the reflected wave returns faster and merges with the forward wave in systole. This adds more BP to the SBP, and this additional increase in SBP is called augmentation pressure (see Figure below). The net result is an increase in afterload and decreased perfusion of coronary and cerebral arteries. Another metric that has been shown to predict CV outcome is augmentation index, which is obtained by dividing augmentation pressure by central pulse pressure, and the ratio is expressed as percentage (augmentation pressure/pulse pressure × 100) ( Fig. 6.1 ).

Central aortic pressure is more predictive of CV events than peripheral BP. An example of this is the CAFÉ (Conduit Artery Functional Evaluation) study , where hypertensive patients were given either atenolol or amlodipine. Central aortic pressure (applanation tonometry) and peripheral BP (electronic device) were measured. Average follow-up after first tonometry measurement was 3 years. The clinical endpoint was all CV events and development of renal impairment. Peripheral BP was similar in both groups; however, central BP was much lower with tonometry. The amlodipine group had lower central BP than atenolol group. The results showed a significant 16 % reduction in the composite CV events in patients treated with amlodipine compared to atenolol group. This study shows that central aortic pressure measurements can reliably determine the clinical outcomes of antihypertensive therapies. Thus, option E is correct. Although, central aortic pressure measurements are superior to peripheral BP measurements, applanation tonometry is expensive and may not be available in all clinic settings.

Aortic stiffness predicts the rate of kidney function loss, and pulse wave velocity (PWV) is one form of assessing aortic stiffness. Which one of the following drugs does NOT improve aortic stiffness in CKD patients ?

Except for sevelamer carbonate (option D), all other therapies have improved PWV and aortic stiffness in CKD and non-CKD patients.

A 72-year-old man with history of HTN and diabetes is brought to your office with complaints of dizziness, lightheadedness, reduced sweating, and occasional incontinence, particularly in morning hours. His wife, a former nurse, takes his BP twice a day. He is on hydrochlorothiazide (HCTZ) 12.5 mg per day. His morning BP on the day of his visit was 130/74 mmHg with heart rate of 68 beats/min (supine) and 100/64 mmHg with heart rate of 67 beats/min (standing). His labs: Na⁺ 136 mEq/L, K⁺ 3.6 mEq/L, HCO₃ ⁻ 28 mEq/L, creatinine 1.4 mg/dL, glucose 140 mg/dL, Ca²⁺ 10.2 mg/dL, and uric acid 8.4 mg/dL. Based upon his BP, heart rate, and electrolyte pattern , which one of the following conditions is MOST likely in this patient?

The patient clearly demonstrates orthostatic hypotension, which is defined as a decrease in SBP of at least 20 mmHg or DBP of 10 mmHg within 3 min of standing. In patients with HTN, a decrease in SBP of 30 mmHg is more appropriate to define orthostatic hypotension. Concomitant measurement of heart rate is extremely important, as orthostatic hypotension due to volume depletion, adrenal insufficiency, and certain medication will increase heart rate upon standing. On the other hand, neurogenic orthostatic hypotension caused by central or peripheral nervous system diseases that result in autonomic failure is not accompanied by a compensatory increase in heart rate. In this patient, the heart rate did not increase despite a fall in both SBP and DBP, suggesting the diagnosis of neurogenic orthostatic hypotension. Thus, option C is correct. The patient’s symptoms are due to his orthostatic hypotension. The electrolyte abnormalities are due to HCTZ and associated volume depletion. Adrenal insufficiency is unlikely in view of normal K ⁺ , elevated HCO ₃ ⁻ and glucose levels.

Orthostatic hypotension in elderly subjects is predisposed to which one of the following conditions?

Orthostatic hypotension, particularly in the elderly with or without HTN, is associated with all of the above conditions, making E as the correct answer.

Which one of the following therapeutic modalities is effective in patients with orthostatic hypotension ?

Pharmacologic interventions include fludrocortisones (increase volume), midodrine (α1-agonist, 5-10 mg once or twice daily), pyridostigmine (anticholinesterase inhibitor, 30-60 mg once or twice daily), octreotide (splanchnic vasoconstrictor, 12.5-25 μg subcutaneously), and pseudoephedrine (30 mg daily) or a combination of fludrocortisone and midodrine, or midodrine, pseudoephedrine, and 16 oz of water. Thus, option E is correct.

Which one of the following drugs does NOT cause neurogenic orthostatic hypotension ?

Except for clonidine, all other drugs cause orthostatic hypotension. Clonidine reduces BP in patients with essential HTN; however, it “paradoxically” raises BP in autonomic failure or hypoadrenergic orthostatic hypotension. The mechanism seems to be arterial and/or venous constriction in patients with neurogenic orthostatic hypotension. Thus, option C is correct.

A 32-year-old man is referred to you for evaluation of newly diagnosed HTN, and you made the diagnosis of essential HTN. Which one of the following pathogenic mechanisms might be involved in the development of his HTN?

In addition, hyperuricemia, metabolic syndrome, and low nephron number have been implicated. It appears that all of the mechanisms cause renal vasoconstriction and renal ischemia, finally resulting in decreased GFR and Na ⁺ retention. The following figure summarizes these mechanisms (Fig. 6.2 ).

A 52-year-old African American woman is seen in your office for the first time for evaluation of a BP of 150/89 mmHg with a heart rate of 64 beats per min (BPM). Physical examination is unremarkable, and serum chemistry is normal. You take a dietary history and she denies high salt intake. You order a 24-h urine Na⁺ and creatinine, and the urine Na⁺ is found to be 140 mEq. According to the DASH (Dietary Approaches to Stop Hypertension ), which one of the following dietary Na ⁺ intake you recommend, in addition to DASH combination diet (diet rich in fruits, vegetable, and low-fat dairy foods with reduced saturated fat and cholesterol) to achieve good BP control in this patient?

The DASH sodium trial tested the effects of three different Na ⁺ intakes separately in two diets: the DASH diet and a typical American (control) diet. From 24-h urinary Na ⁺ determination, the three Na ⁺ levels were termed low (1500 mg or 65 mEq), intermediate (2500 mg or 107 mEq), and high (3300 mg or 142 mEq). The subjects with the lowest intake of Na ⁺ (1500 mg/day) had the lowest BP, as compared with other Na ⁺ intakes. The reduction in BP occurred in both hypertensive and nonhypertensive participants. The combination of DASH diet and low Na ⁺ intake was more effective in lowering BP than either intervention alone. In addition to DASH study, several other studies have documented that low dietary Na ⁺ intake improves BP. Thus, E is correct.

A 50-year-old African American woman with HTN and normal renal function follows DASH combination diet with 1500 mg Na⁺ without any antihypertensive medications. Which one of the following statements is TRUE regarding BP reduction in this woman?

The subgroup analysis of the participants from the DASH studies showed that African Americans with untreated HTN had more BP reduction than whites (E incorrect). In hypertensive African Americans, the BP reduction was 13.2/6.1 mmHg compared to a reduction of 6.3/4.4 mmHg in hypertensive whites. Among normotensive African Americans, the DASH combination diet reduced BP by 4.3/2.6 mmHg compared to 2.0/1.2 mmHg reduction in normotensive white participants. Thus, D is the true statement, and other statements are false. The reduction in BP in hypertensive African Americans is comparable to BP reduction in a patient on 1 antihypertensive drug, as shown in the following table (Table 6.2 ).

Vegetarian diet has been shown to lower BP by which one of the following mechanisms?

A few randomized, controlled studies have shown that patients on vegetarian diets had a lower SBP (5-9 mmHg lower) and a lower DBP (3 mmHg lower) compared to control subjects. In one study with hypertensive patients aged 40-69 years, vegan diet for a year lowered SBP by 9 mmHg and DBP by 5 mmHg. Other studies have shown a BP decrease of 3-14/5-6 mmHg. A recent meta-analysis confirmed that vegetarian diet lowers both SBP and DBP. The mechanisms by which vegetarian diet lowers BP are not fully understood; however, weight loss, high K ⁺ and fiber content with low total fat and low saturated fat may be responsible for lowering BP in both normotensive and hypertensive subjects.

Most of the studies on Na⁺ restriction and BP reduction pertain to patients with normal renal function with normal or high BP. A recent study in CKD 3-4 patients showed that Na ⁺ restriction is NOT beneficial in improving which one of the following risk factors for cardiovascular disease ( CVD ) ?

Studies of Na ⁺ restriction on BP and other risk factors of CVD are limited in patients with CKD 3-4 and HTN. A study by McMahon et al. showed in a double-blind, placebo-controlled, randomized, cross-over trial that CKD 3-4 patients on low Na ⁺ diet (mean Na ⁺ excretion 75 mEq with a range from 58 to 112 mEq) significantly improved BP, proteinuria, albuminuria, and ECF volume compared to high salt intake (mean Na ⁺ excretion 168 mEq with a range from 146 to 219 mEq). However, no effect of low salt diet was observed on PWV (option E). Although the number of patients in this study ( n = 20) is limited, the results are extremely important that low Na ⁺ intake is beneficial in improving risk factors for CV and kidney disease.

Match the following associations between environmental exposure/agents and BP :

Diets rich in K ⁺ are found to lower BP, and BP reduction is more in African Americans compared to whites. High K ⁺ causes vasodilation, thereby reducing BP.

A dose–response relationship between alcohol intake and BP showed that alcohol intake >2 drinks raises BP (1 drink is defined as 1.5 oz of 80 % proof spirits, 12 oz of regular beer, and 5 oz of wine containing 12 % alcohol). Binge drinkers develop severe HTN. HTN due to alcohol is related to overactivity of sympathetic nervous system. Chronic alcoholism leads to persistent HTN.

A scientist friend of yours asks you about garlic and BP. Regarding garlic and BP , which one of the following statements is TRUE?

Intake of fresh garlic or garlic powder has been shown to lower BP, improve hyperlipidemia, prevent cold and bacterial infections, and improve claudication. Garlic seems to generate hydrogen peroxide, which lowers BP by activating ATP gated K ⁺ channels in vascular smooth muscle cells. Also, garlic generates nitric oxide, causing vasodilation and a decrease in BP. Garlic prevents oxidative stress and lipid peroxidation. Thus, garlic lowers BP by multiple mechanisms (E is correct).

Fructose intake in the form of sweetened beverage has been shown to raise BP by which one of the following mechanisms?

A close association between fructose-containing beverages and an incidental and chronic HTN has been repeatedly reported. All of the above mechanisms seem to participate in elevating BP. Na ⁺ absorption in the gut is due to increased Na/H exchanger and Cl/base exchanger of the apical membrane. Fructose causes preglomerular arteriolopathy, cortical vasoconstriction, and glomerular HTN, which subsequently maintain chronic HTN. During the process of fructose metabolism, ATP is consumed to generate AMP, which is converted to uric acid. In addition, fructose causes endothelial dysfunction, resulting in high BP. Thus, option E is correct.

A 66-year-old African American man is referred to you for management of HTN. Despite dietary Na⁺ restriction (2 g Na⁺ diet or 88 mEq) and chlorthalidone (25 mg), his BP is not well controlled. He has a strong family history of stroke. His glucose and creatinine are normal. The patient is concerned about future stroke, if his BP is not controlled. In view of the above information, which one of the following drugs reduces stroke risk in this patient?

Studies have shown that CCBs are better than ACE-Is for stroke outcomes in African Americans. However, ACE-Is are better than CCBs for heart failure outcomes. In both African Americans and non-African Americans, ACE-Is and CCBs are similar with respect to overall mortality and renal outcomes.

A 72-year-old man with BP of 168/94 mmHg is treated with chlorthalidone (25 mg daily). Lowering his BP to <150/90 mmHg by addition of amlodipine reduces which one of the following cardiac- and cerebrovascular outcomes ?

Initiating pharmacologic therapy with antihypertensive agents to a goal BP <150/90 mmHg in persons 60 years or older with a SBP ≥160 mmHg has been shown to reduce cerebrovascular morbidity and mortality (fatal stroke, nonfatal stroke, or both), fatal and nonfatal heart failure, overall mortality, and CHD (CHD mortality, fatal MI, nonfatal MI). Thus, E is correct.

Initiating pharmacologic treatment in a 42-year-old woman with DBP of 96 mmHg would likely reduce which one of the following cardiac- and cerebrovascular outcome ?

According to JNC 8 guideline, there is moderate to high evidence that treating DBP ≥90 mmHg in adults 30 years of age or older reduces cerebrovascular morbidity and mortality (fatal stroke, nonfatal stroke, or both), and heart failure. However, there is insufficient evidence for fatal MI and mortality from CHD. Thus, E is correct

Match the following characteristics of hypertensive patients with the goal BPs, as suggested by JNC 8 (select the same BP, if applicable)

According to JNC 8 guideline, the goal BP in patients ≥60 years is <150/90 mmHg, whereas in patients <60 years of age it is <140/90 mmHg. In patients with CKD and diabetes, the goal BP is <140/90 mmHg. Other guidelines by KDIGO (Kidney Disease Improving Global Outcome, 1212) and ISHIB (International Society for Hypertension in Blacks, 2010), the goal BP in CKD patients with proteinuria, and in African Americans with target organ damage is 130/80 mmHg. The American Diabetes Association (2013) recommends a goal BP <140/80 mmHg for diabetic patients.

You are consulted on a 28-year-old man with IgA nephropathy and proteinuria of 1.2 g/day. His BP is 134/84 mmHg with a heart rate of 70 BPM. His creatinine is 1.0 mg/dL. He has no insurance. Which one of the following medications you recommend to improve his proteinuria ?

The JNC 8 and other position statements recommend either an ACE-I or an ARB for patients with CKD and proteinuria as the drug of choice. Lisinopril costs less compared to other ACE-Is. Thus, C is correct. Amlodipine, chlorthalidone, and atenolol can be added, as needed, to control HTN. Prednisone is not indicated in this patient, as ACE-Is or ARBS can improve proteinuria and also BP.

You see this patient in your office 4 weeks later. Repeat labs show no change other than an increase in serum creatinine from 1.0 to 1.2 mg/dL. His proteinuria decreased from 1.2 g to 0.9 g/day. He is euvolemic. What is your next step in the management of this patient ?

The patient is responding to lisinopril by improving his proteinuria. An increase in creatinine up to 30 % in response to ACE-Is or ARBs is common, indicating a decrease in glomerular HTN and glomerular filtration. This is a reversible physiologic response and is not harmful. ACE-Is and ARBs also increase serum [K ⁺ ]. The best thing to do is to continue lisinopril and follow serum chemistry and proteinuria. Thus, C is correct. Other options are not appropriate for this patient at this time.

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