Hypertension, Secondary and Resistant



Uncontrolled hypertension (HTN) comprises the following entities (see “Alert” below):

  • Resistant HTN: defined as blood pressure (BP) that remains above goal in spite of the concurrent use of three antihypertensive agents of different classes. Ideally, one of the three agents should be a diuretic, and all agents should be prescribed at optimal dose amounts. The diagnosis should not include “white-coat effect” or medication nonadherence, although these are common mimics.
  • Secondary HTN: elevated BP that results from an identifiable underlying mechanism
  • The 2017 revised ACC/AHA guideline recommends a change in the classification of HTN. For the purposes of this chapter, we are considering stage 2 HTN: systolic blood pressure (SBP) ≥140 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg. The guideline is quite controversial (1). See “Hypertension, Essential” topic. Many experts still adhere to the JNC 8 guideline, which allows for a goal of <150/90 mm Hg for patients age >60 years, and do not agree with a diagnosis or class of HTN for pressures below 140/90 (2)[C].
    Geriatric Considerations
    • Onset of HTN in adults >60 years of age is a strong indicator of secondary HTN.
    • In patients >80 years of age, consider a higher target SBP of ≥150 mm Hg. Be cautious to avoid excessive diastolic lowering.
    • Elderly may be particularly responsive to diuretics and dihydropyridine calcium channel blockers.
    • Systolic HTN is particularly problematic in the elderly.
    • Secondary causes more common in the elderly include sleep apnea, renal disease, atherosclerotic renal artery stenosis, and primary aldosteronism (PA).
    • Noncompressible arteries (Osler phenomenon)—mostly in elderly with arteriosclerosis: Brachial and radial artery pulsations are present at high cuff pressures.
  • Inaccurate measurement of BP
    • Cuff too small
    • Patient not at rest; sitting quietly for 5 minutes
  • Poor adherence: In primary care settings, this has been estimated to occur in 40–60% of patients with HTN.
  • White coat effect: prevalence 20–40%. Do not make clinical decisions about HTN based solely on measurement in the clinic setting. Home BP monitoring and/or ABPM is more reliable. See USPSTF and AHA recommendations (3).
    • Automated office blood pressure (AOBP) is the preferred method of measurement. If AOBP is not possible, home blood pressure measurement (HBPM) is preferred when making decisions about treatment.
  • Inadequate treatment


  • Predominant age: In general, HTN has its onset between ages 30 and 50 years. Patients with resistant HTN are more likely to experience the combined outcomes of death, myocardial infarction, congestive heart failure (CHF), stroke, or chronic kidney disease.
  • Depending on etiology, age of onset can vary. Age of onset <20 or >50 years increases likelihood of a secondary cause for HTN.
  • The strongest predictors for resistant HTN are age (>75 years), presence of left ventricular hypertrophy (LVH), obesity (body mass index [BMI] >30), and high baseline SBP. Other predictors include chronic kidney disease, diabetes, living in the Southeastern United States, African American race (especially women), and excessive salt intake.

The age-standardized incidence in the United Kingdom is 0.4 cases per 100 person-years in 2015. Information in the United States is less clear (4).


  • Prevalence of resistant HTN is estimated to be 10–15% in clinic-based reports (5). NHANES analysis indicates only 53% of adults are controlled to a BP of <140/90 mm Hg. The most common cause of apparently resistant hypertension is likely medication nonadherence.
  • Secondary HTN occurs in about 5–10% of adults with chronic HTN.

Etiology and Pathophysiology

  • Obstructive sleep apnea (25–50%): Results of interventions have been mixed.
  • Primary hyperaldosteronism (8–20% of resistant HTN cases)
  • Chronic renal disease (1–2% of hypertensives)
  • Renovascular disease (0.2–0.7%, up to 35% of elderly, 20% of patients undergoing cardiac catheterization)
  • Cushing syndrome (<0.1%)
  • Pheochromocytoma (0.04–0.1% of hypertensives)
  • Other rare causes: hyperthyroidism, hyperparathyroidism, aortic coarctation, intracranial tumor
  • Drug-related causes
    • Medications, especially NSAIDs (may also blunt effectiveness of ACE inhibitors), decongestants, stimulants (e.g., amphetamines, attention deficient hyperactivity disorder [ADHD] medications), anorectic agents (e.g., modafinil, ephedra, guarana, ma huang, bitter orange), erythropoietin, natural licorice (in some chewing tobacco), yohimbine, glucocorticoids
    • Oral contraceptives (OCP): Women taking oral contraceptives may have more severe HTN and poorer BP control, primarily correlated with the estrogen content. Cessation of OCP may result in normalization of the BP. Postmenopausal estrogen does not appear to correlate as strongly (5).
    • Cocaine, amphetamines, other illicit drugs; drug and alcohol withdrawal syndromes
  • Lifestyle factors: Obesity and dietary salt may negate the beneficial effect of diuretics. Excessive alcohol may cause or exacerbate HTN. Physical inactivity also contributes.

BP has a genetic basis: It is heritable and more prevalent in certain families. Genetic variants have been detected in patients with resistant HTN but are estimated to account for <3% of BP variance (5).

Risk Factors

A large cohort study revealed that those with resistant HTN (16.2%) were more likely to be male, Caucasian, older, and diabetic. They were also more likely to be taking β-blockers, calcium channel blockers, and α-adrenergic blockers compared with other drug classes. Factors predictive of resistant or secondary HTN: obesity, diabetes, worsening of control in previously stable hypertensive patient, onset in patients age <20 years or >50 years, lack of family history of HTN, significant target end-organ damage, stage 2 HTN (SBP >160 mm Hg or DBP >100 mm Hg), renal disease, and alcohol or drug use

General Prevention

The prevention of resistant and secondary HTN is thought to be the same as for primary or essential HTN: Adopting a Dietary Approaches to Stop Hypertension (DASH) diet, a low-sodium diet, weight loss in obese patients, exercise, limitation of alcohol intake, and smoking cessation may all be of benefit. Relaxation techniques may be of help, but data are limited.

Commonly Associated Conditions

Sleep disorders; obesity

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