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The pathophysiology of hypertension involves the impairment of renal pressure natriuresis, the feedback system in which high blood pressure induces an increase in sodium and water excretion by the kidney that leads to a reduction of the blood pressure. Pressure natriuresis can result from impaired renal function, inappropriate activation of hormones that regulate salt and water excretion by the kidney (such as those in the renin-angiotensin-aldosterone system), or excessive activation of the sympathetic nervous system.

Widespread human primary (essential) hypertension appears to be associated with industrialization.

Nearly all studies of industrialized populations have demonstrated that BP and the prevalence of hypertension increase with age.1 Hunter-gatherers living in nonindustrialized societies, however, rarely develop hypertension or progressive increases in systolic and mean pressures that occur in the majority of individuals living in industrialized societies.182 This observation suggests that environmental factors play a major role in increasing BP in many patients with primary hypertension.

This does not, however, imply that genetic factors are unimportant in primary hypertension. Genetic variation is responsible for differences in baseline BP that result in normal BP distribution in a population. When hypertension-producing environmental factors are added to the population baseline BP, the normal distribution is shifted toward higher BP. Moreover, variations in the impact of environmental factors flatten the BP curve and cause even greater variability in the overall population BP.

What are the factors that cause BP to increase in the majority of people as they age in industrialized societies? How do they affect the physiologic controllers of BP?

As discussed earlier, many of the long-term BP controllers either directly or indirectly influence renal function. In patients with primary hypertension, there is a resetting of renal pressure natriuresis so that sodium balance is maintained at higher BP.12,21 In some individuals, this resetting is related to increased renal tubular reabsorption because of abnormalities intrinsic to the kidneys or to altered neurohumoral control of the kidneys. In other instances, resetting of pressure natriuresis is associated with renal vasoconstriction and reductions in GFR, as a result of intrarenal mechanisms or of nervous and hormonal mechanisms acting on the kidneys. After hypertension is established, many of these changes are difficult to detect because increased BP often returns renal function to normal.

Some of the key environmental factors that affect BP include excess weight gain, high sodium intake, and excess alcohol intake.

Excess Weight Gain is a Major Cause of Primary Hypertension

Current estimates indicate that more than 1.4 billion people in the world are overweight or obese.183 In the United States, more than 67% of adults are overweight, and one-third of the adult population is obese, with body mass indices (BMIs) above 30.184 Population studies show that excess weight gain is a good predictor for development of hypertension, and the relationship between BMI and systolic and diastolic BP is nearly linear in diverse populations throughout the world.50,185 Risk estimates from the Framingham Heart Study, for example, suggest that approximately 78% of primary hypertension in men and 65% in women can be ascribed to excess weight gain.186 Clinical studies indicate that maintenance of a BMI less than 25 kg/m2 is effective in primary prevention of hypertension and that weight loss reduces BP in most hypertensive subjects.187,188

One question often raised is why some overweight or obese persons are not hypertensive by the usual standards (ie, BP > 140/90 mm Hg) if obesity is a major cause of hypertension. Perhaps this is not surprising if one considers that BP is normally distributed and that excess weight gain shifts the frequency distribution of BP toward higher levels (Fig. 24–15). However, even obese individuals who are considered “normotensive” have higher BP than they would at a lower body weight, and weight loss lowers BP in normotensive as well as hypertensive obese subjects.189



Which of the following antihypertensive medications should not be used as a first-line treatment for a person with essential hypertension and no other medical conditions?

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The correct answer is B. You answered B.

Answer: B

According to the 2017 American College of Cardiology (ACC) guidelines and the 2014 Joint National Committee (JNC) guidelines, thiazide diuretics or calcium channel blockers are generally considered first-line options for therapy in all persons with hypertension. ACE inhibitors and angiotensin receptor blockers (ARBs) are also recommended as options in non-black patients. This is a departure from prior recommendations when ACE inhibitors and ARBs were routinely recommended as first-line therapy for Caucasian patients. Beta blockers (unless there are other factors such as a history of coronary artery disease or cardiac arrhythmias) are not recommended for routine first-line therapy of essential hypertension.

References: Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018;71(19):e127-e248.1. Pubmed ID: 29146535.

James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-520. Pubmed ID: 24352797.


A 75-year-old triathlete complains of gradually worsening vision over the past year. It seems to be involving near and far vision. The patient has never required corrective lenses and has no significant medical history other than diet-controlled hypertension. He takes no regular medications. Physical examination is normal except for bilateral visual acuity of 20/100. There are no focal visual field defects and no redness of the eyes or eyelids. Which of the following is the most likely diagnosis?

Age-related macular degeneration


Diabetic retinopathy


Retinal detachment

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The correct answer is A. You answered A.

Age-related macular degeneration is a major cause of painless, gradual bilateral central visual loss. It occurs as nonexudative (dry) or exudative (wet) forms. Recent genetic data have shown an association with the alternative complement pathway gene for complement factor H. The mechanism link for that association is unknown. The nonexudative form is associated with retinal drusen that leads to retinal atrophy. Treatment with vitamin C, vitamin E, beta-carotene, and zinc may retard the visual loss. Exudative macular degeneration, which is less common, is caused by neovascular proliferation and leakage of choroidal blood vessels. Acute visual loss may occur because of bleeding. Exudative macular degeneration may be treated with intraocular injection of a vascular endothelial growth factor antagonist (bevacizumab or ranibizumab). Blepharitis is inflammation of the eyelids usually related to acne rosacea, seborrheic dermatitis, or staphylococcal infection. Diabetic retinopathy, now a leading cause of blindness in the United States, causes gradual bilateral visual loss in patients with long-standing diabetes. Retinal detachment is usually unilateral and causes visual loss and an afferent pupillary defect.


Mr. Jenson is a 40-year-old man with a congenital bicuspid aortic valve who you have been seeing for more than a decade. You obtain an echocardiogram every other year to follow the progression of his disease knowing that bicuspid valves often develop stenosis or regurgitation requiring replacement in middle age. Given his specific congenital abnormality, what other anatomic structure is important to follow on his biannual echocardiograms?

Aortic root size

Left atrial size

Pulmonary artery pressures

Pulmonic valve function

Tricuspid valve regurgitation

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The correct answer is A. You answered A.

The answer is A. (Chap. 282) Bicuspid aortic valve is among the most common of congenital heart cardiac abnormalities. Valvular function is often normal in early life and thus may escape detection. Due to abnormal flow dynamics through the bicuspid aortic valve, the valve leaflets can become rigid and fibrosed, leading to either stenosis or regurgitation. However, pathology in patients with bicuspid aortic valve is not limited to the valve alone. The ascending aorta is often dilated, misnamed “poststenotic” dilatation; this is due to histologic abnormalities of the aortic media and may result in aortic dissection. It is important to screen specifically for aortopathy because dissection is a common cause of sudden death in these patients.



The primary goal of antihypertensive therapy is to reduce stroke, heart failure, and CAD. In addition, the morbidity and mortality associated with renal disease is also worsened by hypertension. According to the 2017 ACC/AHA hypertension guidelines, the treatment goal for most individuals is to get the systolic blood pressure (SBP) below 130 mm Hg and diastolic blood pressure (DBP) below 80 mm Hg.1 BP values greater than 130/80 mm Hg have been associated with a decrease in stroke, heart failure, and CAD. Note that this is a change from the JNC 8 2013 target of SBP below 140 mm Hg and DBP below 80 mm Hg.2 Also note that the threshold for stage 2 hypertension in the ACC/AHA 2017 guidelines is lower than previously recommended levels of 160 mm Hg (SBP) and 100 mm Hg (DBP). Also, unlike the JNC 8 guidelines, the ACC/AHA 2017 guidelines do not use age-differentiated cut points to define hypertension. In the ACC/AHA 2017 guidelines, the categories of BP are for “adults,” without any reference to age.

Content 2

There is no proven benefit to the rapid reduction of BP in patients with severe asymptomatic HTN. The initial goal of therapy in these patients should be to achieve a diastolic BP of 100 to 110 mm Hg. A rapid decrease in BP may cause cerebral hypoperfusion or coronary insufficiency. The target BP can be achieved over several days.

Hypertensive emergencies warrant admission to an ICU and treatment with parenteral agents. In an emergency situation, control of acute or ongoing end-organ damage is more important than the absolute level of BP. BP control with rapidly acting IV agent should be administered within 1 hour to reduce permanent organ damage or death. A reasonable target is a 20% to 25% reduction of mean arterial pressure (MAP) or reduction of diastolic BP to 100 to 110 mm Hg over a period of minutes to hours. Precautions should be taken in patients who are elderly, volume depleted, or receiving other antihypertensive agents to avoid cerebral hypoperfusion (Tables 30-230-330-4).

Clinical Perspective


According to 2017 ACC/AHA Guidelines1:

  • Normal blood pressure SBP less than 120 mm Hg and DBP less than 80 mm Hg

  • Elevated blood pressure is SBP between 120 and 129 mm Hg and DBP less than 80 mm Hg

  • Stage 1 HTN is SBP between 130 and 139 mm Hg or DBP between 80 and 89 mm Hg

  • Stage 2 HTN is SBP greater than 140 mm Hg or DBP greater than or equal to 90 mm Hg

The 2017 guidelines recommend the following treatment and follow-up based on the severity of the blood pressure elevation and an estimated 10-year ASCVD risk.1

  • For patients with elevated blood pressure or stage 1 hypertension with an estimated 10-year ASCVD risk of less than 10%, nonpharmacologic therapy (lifestyle modifications) is recommended with a repeat BP evaluation in 3 to 6 months.

  • For patients with stage 1 hypertension and an estimated 10-year ASCVD risk greater than or equal to 10%, a combination of lifestyle modifications and 1-drug treatment is recommended with follow-up blood pressure evaluation in a month.

  • For patients with stage 2 hypertension, in addition to lifestyle modifications, the recommended treatment is to use 2 drugs from different classes with a recheck of blood pressure in a month.

  • For adults with very high average BP (eg, SBP greater than 180 mm Hg or DBP greater than 110 mm Hg), the recommendation is evaluation followed by prompt antihypertensive drug treatment.

  • Adults with well controlled hypertension can be followed annually.

(nb: The 2017 American Diabetes Association (ADA) recommendations for blood pressure treatment goals for persons with diabetes were aligned with the JNC 8 treatment goals and are currently being updated. The current ADA’s treatment goals stated that a BP target of less than 130 mm Hg SPB and less than 80 mm Hg DBP “may be appropriate for certain patients, including younger patients, if they can be achieved without undue treatment burden.”3



Key points on how to take an accurate BP are:

  • Properly prepare the patient.

    • The patient should be seated with both feet on the floor, back against the chair for more than 5 minutes before the blood pressure is taken; measurements made while the patient is sitting or lying on an exam table do not fulfill the criteria.

    • The patient’s bladder should be emptied.

    • Any clothing covering the area where the cuff will be placed should be removed.

    • Neither the patient nor the observer should talk during the measurement.

  • Use proper technique for BP measurements.

    • The patient’s bare arm should be supported at the level of the heart.

    • Choose the appropriate-sized cuff. A cuff that is too large can underestimate the blood pressure, and a cuff that is too small can overestimate the blood pressure.

    • Place the cuff so that the bladder of the cuff is over the brachial artery.

    • Rapidly inflate the cuff to 70 mm Hg and increase by 10 mm Hg increments while palpating the radial pulse. Note the pressure at which the radial pulse disappears and subsequently reappears during cuff deflation (“palpatory method” to better estimate adequate inflation—avoiding overinflation in persons with low blood pressure and underinflation in those with an auscultatory gap).

    • Use either the bell or the diaphragm of the stethoscope over the brachial artery and below the cuff (not wedged under the cuff).

    • Inflate the cuff to 20 to 30 mm Hg above the palpated pulse disappearance pressure and deflate the bladder at 2 mm Hg/sec while listening for the appearance and disappearance of the Korotkoff sounds.

      • Phase I = appearance of the first sounds = systolic blood pressure (SBP)

      • Phase V = disappearance of the Korotkoff sounds =diastolic blood pressure (DBP)

  • Take the proper measurement needed for diagnosis and treatment of elevated BP or hypertension.

    • At the first visit, record BP in both arms; use the arm that gives the higher reading for subsequent readings.

    • Separate measurements by one to two minutes.

    • Round off (upward) to the nearest even number

    • Measurement should be repeated after one to two minutes and the two readings averaged

  • Properly document accurate BP readings.

  • Average the readings.

    • Average more than two readings obtained on more than two occasions to estimate the BP.

  • Provide BP readings to the patient.

    • SBP and DBP readings should be provided verbally and in writing to the patient.



For patients with diabetes, his blood pressure target is <130/80 mm Hg.1

The BP goal for the general population is <140/90 mm Hg.

dietary changes including decrease of sodium intake to less than 2400 mg per day and adoption of the DASH (Dietary Approaches to Stop Hypertension) diet, which is rich in fruits, vegetables, and potassium and low in saturated fats.

Weight loss for those who are overweight and aerobic exercise most days of the week for 20 to 30 minutes are also recommended.

Patients with diabetes and hypertension should be treated with ACE inhibitors or angiotensin receptor blockers (ARBs) as they help delay the onset and progression of diabetic nephropathy.

All patients with a new diagnosis of HTN should be assessed for organ damage and the presence of other cardiovascular risk factors. Complete blood count (CBC), basic metabolic profile (BMP), urinalysis (for microalbuminuria), EKG, lipid profile, and fasting blood sugar (or HbA1C) should be obtained at the time of diagnosis.

The Seventh Report of the JNC-7 defines hypertension as systolic pressure ≥140 mm Hg or diastolic pressure ≥90 mm Hg for the general population, and ≥130 or ≥80 mm Hg for certain groups including patients with diabetes and chronic kidney disease.



The most effective two-drug combinations:

consist of a renin-system blocking agent (angiotensin-converting enzyme inhibitor [ACEI] or angiotensin-receptor blocker [ARB]) and a thiazide-type diuretic or

a renin system blocker and a calcium channel blocker (CCB).

When the two-drug combination is not fully effective, adding the third component will often be successful (ie, renin system blocker, diuretic, and CCB).

The benefit of adding a drug class appears to be substantially greater than up-titrating dosage with a single drug class. 59

Drug classes to be prescribed to achieve control of hypertension (see Table 25–4).


Hypertension leads to myocardial infarction, stroke, renal failure, and death if not detected early and treated appropriately.

Hypertension is the most common condition seen in primary care.

Based on data from the 2011–2012 NHANES survey, about one-third of adults in the United States are hypertensive. Hypertension is uncontrolled in almost half of these 71 million people, and of those with uncontrolled hypertension, about 36% or 13 million are unaware of the diagnosis.

Even in patients in whom hypertension is diagnosed and treated, control is attained in only 60%. By convention, hypertension is categorized based on office measurements as stage 1 (140–159/90–99 mm Hg) and stage 2 (greater than 160/100 mm Hg). Cardiovascular morbidity and mortality increase as both systolic and diastolic blood pressures rise, but in individuals over age 50 years, the systolic pressure and pulse pressure are better predictors of complications than diastolic pressure. The prevalence of hypertension increases with age, and it is more common in blacks than in whites. Adequate blood pressure control reduces the incidence of acute coronary syndrome by 20–25%, stroke by 30–35%, and heart failure by 50%.

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