Description

Uncontrolled HTN is composed of the following entities:

• Resistant hypertension: Defined by the US Joint National Committee 7 (JNC-7)as “failure to achieve goal BP (<140/90 mm Hg for the overall population and <130/80 mm Hg for those with diabetes or chronic kidney disease) when a patient adheres to maximum tolerated doses of 3 antihypertensive drugs including a diuretic” (1,2,3)
• Secondary hypertension: Elevated BP that results from an identifiable underlying mechanism (1,2)

• Onset of hypertension 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 (4).
• Elderly may be particularly responsive to diuretics and dihydropyridine calcium channel blockers (4).
• 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 (2).

• 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 (2).
• 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 (5).
• Inadequate treatment (2)

Epidemiology

• Predominant age: In general, HTN has its onset between ages 30 and 50. Patients with resistant hypertension are more likely to experience the combined outcomes of death, myocardial infarction, congestive heart failure (CHF), stroke, or chronic kidney disease (3).
• Depending on etiology, age of onset can vary. Age of onset <20 years or >50 years increases likelihood of a secondary cause for HTN.
• The strongest predictors for resistant HTN are age (>75), 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 US, African American race (especially women), and excessive salt intake (2).
• In the ACCOMPLISH, INVEST, CONVINCE, ALLHAT, and LIFE studies, percent of patients reaching JNC-7 BP goals ranged from 45–82% (1).

• Obstructive sleep apnea (OSA): 1 study diagnosed OSA in 83% of treatment-resistant hypertensives (2).
• Primary hyperaldosteronism (17–22% of resistant HTN cases) (2)
• Chronic renal disease (2–5% of hypertensives)
• Renovascular disease (0.2–0.7%, up to 35% of elderly, 20% of patients undergoing cardiac catheterization) (2)
• Cushing syndrome (0.1–0.6%)
• Pheochromocytoma (0.04–0.1% of hypertensives)

Risk Factors

A recent large cohort study revealed that those with resistant hypertension (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 (3). Factors predictive of resistant or secondary hypertension: Female sex, African-American race, obesity, diabetes, worsening of control in previously stable hypertensive patient, onset in patients age <20 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

Genetics
In some patients, there is a possible relationship to ENaC gene variants (Liddle syndrome) and a CYP3A5 allele (cortisol metabolism, especially African Americans) (2).

General Prevention

The prevention of resistant and secondary HTN is thought to be the same as for primary or essential HTN. Adopting a DASH (Dietary Approaches to Stop Hypertension) 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.

Pathophysiology

Depends on underlying etiology

Etiology

• 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, dietary salt may negate the beneficial effect of diuretics. Excessive alcohol, physical inactivity also contributors