The dilemma of pseudo resistance
Pseudo resistance refers to poorly-controlled HT that appears to be resistant, but in fact its resistance is attributable to factors other than inability to control BP with medication or lifestyle changes. Such factors include:
- inaccurate BP measurement
- white coat HT
- failure to detect a secondary cause, such as primary aldosteronism, or; poor adherence to therapy.7, 17-19
A careful evaluation must exclude these factors before labeling a patient with RH.
Although guidelines are available to properly assess office BP readings, several mistakes often produce falsely elevated readings. The three most common mistakes in BP measurement include: a) measuring the BP before letting the patient sit quietly for five minutes; b) taking only a single reading in one arm, and; c) inappropriately using a small arm cuff for a larger arm circumference.7,19
Other BP reading errors can be triggered by a patient’s smoking prior to measurement, and if the clinician does not fully supporting the patient’s arm at heart level.20 In the elderly, presence of highly-calcified or arteriosclerotic arteries results in the overestimation of intra-arterial BP.21
Poor adherence to antihypertensive therapy is another cause of presumed RH. Studies suggest that up to 40% of patients with newly diagnosed HT will discontinue their medications during the first year of treatment.22,23 In surveillance of over 4,000 patients, a 50% antihypertensive discontinuation rate was seen within the first year of treatment.24 Factors that may improve medication adherence by patients are listed in Table 1.
A notable contributing factor to pseudo resistance is clinical inertia among physicians. Clinical inertia is defined as a conscious decision not to adequately treat a condition despite knowing that the disease is present.25 Lack of training and experience on the proper use of antihypertensive agents, or an overestimation of the care already provided may be factors here.26
Poor adherence to medication is typically seen at all levels of practice, and is less common in referral practices of board certified clinical HT specialists (Garg/Singer papers). In a retrospective study at a HT specialty clinic, poor medication adherence is seen in only 16% of the evaluated patients.7
Once factors contributing to pseudo resistant HT are identified, the problem is easily correctable. To encourage better adherence, make the patient responsible for his/her disease. Improved adherence is well documented with home BP determination and having the patient report to a healthcare professional at regular intervals. The use of 24-hour ambulatory measurements to rule out white coat effect or masked HT is also important.
Factors in development
Several factors may contribute to the development of RH. Certain classes of pharmacologic agents produce transient or even persistent elevations of BP. Non-steroidal anti-inflammatory drugs (NSAIDs) hinder BP control.27 Meta-analyses of their effects have indicated average increases in mean arterial pressure of approximately 5.0 mm Hg. NSAIDs can also blunt the BP-lowering effects of several antihypertensive medications, with the exception of calcium channel blockers (CCB).28 Similar effects have been seen with selective cyclooxygenase-2 inhibitors.29
These effects presumably occur secondary to the inhibition of renal prostaglandin production, particularly prostaglandin E2 and prostacyclin, with subsequent sodium and fluid retention. Sympathomimetics, such as nasal decongestants and anorexic pills, oral contraceptives, glucocorticoids, erythropoietin, and cyclosporine can also interfere with BP control. Black licorice found in oral tobacco products and herbal supplements, such as ma Huang, increase BP by suppressing the metabolism of cortisol, resulting in the increased stimulation of mineralocorticoid receptors. Illicit drugs, such as cocaine and amphetamines, are also common causes of RH.7, 25
Excess dietary salt is a key and, perhaps, the most important factor responsible for many cases of RH by directly increasing BP through volume overload, and blunting the BP-lowering effect of most classes of antihypertensive agents except CCBs and diuretics.
The majority of patients with RH have higher salt intake than the general population, ex-ceeding more than 10 grams/day.30-32 The effects of increased dietary salt intake tend to be more pronounced in salt- sensitive patients, including the elderly, African Americans, and stage 3 or higher CKD patients.
While modest alcohol consumption does not generally increase BP, heavy alcohol intake (>3 to 4 drinks of “hard liquor”/day) has a dose-related effect on BP, both on normal and hypertensive individuals.33 In an analysis of Chinese adults ingesting >30 drinks per week, the risk of having HT increased from 12% to 14%. Cessation of heavy alcohol ingestion reduced 24-hour ambulatory SBP measurements in such patients by 7.2 mm Hg, and DBP by 6.6 mm Hg.34
Obesity is a very common feature in patients with RH. Most obese patients tend to have an increased need of antihypertensive medications and increased likelihood of never achieving BP control. Mechanisms of obesity-induced HT are complex and not fully understood. Contributing factors in such patients include insulin resistance and hyperinsulinemia, with consequent impairment of sodium excretion, increased sympathetic nervous system activity, increase in aldosterone production by adipocytes, and presence of OSA and sleep disturbances.35-37