Hypertension, Secondary and Resistant

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

  • Resistant HTN: defined as blood pressure 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 (1)[C].
  • Secondary HTN: elevated BP that results from an identifiable underlying mechanism (1)
  • Both the Eighth Joint National Committee (JNC 8) and AHA/ACC/CDC guidelines recommend a goal BP of <140/90 mm Hg, although JNC 8 allows for a goal of <150/90 mm Hg for patients age >60 years (2,3)[C].
  • The SPRINT study suggests that a lower blood pressure may be preferable in some high-risk patients. This is controversial and evolving (4)[B].
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 systolic blood pressure (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, renal artery stenosis, and primary aldosteronism (PA).
  • 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 ambulatory BP monitoring is more reliable. See USPSTF recommendations.
  • 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 systolic BP. Other predictors include chronic kidney disease, diabetes, living in the southeastern United States, African American race (especially women), and excessive salt intake.

  • Prevalence of resistant HTN is unknown. NHANES analysis indicates only 53% of adults are controlled to a BP of <140/90 mm Hg.
  • Secondary HTN occurs in about 5–10% of adults with chronic HTN.

Etiology and Pathophysiology

  • Obstructive sleep apnea (OSA): One study diagnosed OSA in 83% of treatment-resistant hypertensives.
  • Primary hyperaldosteronism (17–22% of resistant HTN cases)
  • Chronic renal disease (2–5% of hypertensives)
  • Renovascular disease (0.2–0.7%, up to 35% of elderly, 20% of patients undergoing cardiac catheterization)
  • Cushing syndrome (0.1–0.6%)
  • 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: unclear association; mainly epidemiologic and with higher estrogen pills
    • 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.

Risk Factors

A recent 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: female sex, African American race, 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 (systolic BP >160 mm Hg or diastolic BP >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.

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TY - ELEC T1 - Hypertension, Secondary and Resistant ID - 117260 ED - Baldor,Robert A, ED - Domino,Frank J, ED - Golding,Jeremy, ED - Stephens,Mark B, BT - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117260/all/Hypertension__Secondary_and_Resistant PB - Wolters Kluwer ET - 27 DB - Medicine Central DP - Unbound Medicine ER -