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Cardio Diabetes Medicine 2017 99

itors, angiotensin receptor blockers (ARBs), and and peripheral resistance as well as by increased flu-
β-blockers. id retention.

Although NSAIDs have an overall modest effect on
blood pressure levels, in susceptible individuals sig- Primary Aldosteronism
nificant fluid retention, increases in blood pressure, Primary aldosteronism is common in patients with
and/or acute kidney disease may occur. These ef- resistant hypertension with a prevalence of approxi-
fects occur secondary to inhibition of renal prosta- mately 20%, based on suppressed renin activity and
glandin production, especially prostaglandin E2 and a high 24-hour urinary aldosterone excretion in the
prostaglandin I2, with subsequent sodium and fluid course of a high dietary sodium intake.
retention. Elderly patients, diabetics, and patients Generalized activation of the renin-angiotensin-al-
with CKD are at increased risk of manifesting these dosterone system has been described with obesity,
adverse effects.
while other studies suggest that adipocytes may re-
Other medications are sympathomimetic compounds lease secretagogues that stimulate aldosterone re-
such as decongestants and certain diet pills, amphet- lease independent of angiotensin-II.
amine-like stimulants, modafinil39, and oral contra-
ceptives. Glucocorticoids, such as prednisone, induce Pheochromocytoma
sodium and fluid retention and can result in signifi- Pheochromocytoma represents a small but important
cant increases in blood pressure. Corticosteroids with fraction of secondary causes of resistant hyperten-
the greatest mineralocorticoid effect (eg, cortisone, sion. The prevalence of pheochromocytoma is 0.1% to
hydrocortisone) produce the greatest amount of fluid 0.6% of hypertensives in a general ambulatory pop-
retention, but even agents without mineralocorticoid ulation. The occurrence of a sustained increase and
activity (eg, dexamethasone, triamcinolone, beta- the degree of blood pressure variability are related to
methasone) produce some fluid retention. Herbal the level of norepinephrine secretion by the tumor.
preparations containing ephedra (or ma huang) have
been associated with worsening blood pressure. Lic- Thediagnosis of pheochromocytoma should be en-
orice, a common ingredient in oral tobacco products, tertained in a hypertensive patient with a combina-
can raise blood pressure by suppressing the metab- tion of headaches, palpitations, and sweating, typi-
olism of cortisol, resulting in increased stimulation cally occurring in an episodic fashion.
of the mineralocorticoid receptor. In anemic patients The best screening test for pheochromocytoma is
with CKD, erythropoietic agents may increase blood plasma free metanephrines (normetanephrine and
pressure in both normotensive and hypertensive pa- metanephrine), which carries a 99% sensitivity and
tients. an 89% specificity.

Secondary Causes Cushing ’s syndrome
Secondary causes of hypertension in patients with Hypertension is present in 70% to 90% of patients
resistant hypertension, are older patients with great- with Cushing’s syndrome. Although the main mech-
er prevalence of sleep apnea, renal parenchymal anism of hypertension in Cushing’s syndrome is
disease, renal artery stenosis, and possibly primary overstimulation of the nonselective mineralocorticoid
aldosteronism.Others, include pheochromocytoma, receptor by cortisol, other factors such as sleep ap-
Cushing’s syndrome, hyperparathyroidism, aortic nea and the insulin resistance syndrome are major
coarctation, and intracranial tumors. contributors to hypertension in this disease.

Obstructive Sleep Apnea Although the exact prevalence of resistant hyper-
tension in patients with Cushing’s syndrome is un-
There was a significant gender difference, with sleep known, the overall CV risk in Cushing’s syndrome is
apnea being more common and more severe in the substantial because the disorder is associated with
men compared with women patients. other major risk factors such as diabetes mellitus,
A well-described effect is that the intermittent hy- the metabolic syndrome, sleep apnea, obesity, and
poxemia, and/or increased upper airway resistance dyslipidemia, in addition to hypertension.
associated with sleep apnea, induces a sustained in- Surgical excision of an adrenocorticotropic hormone
crease in sympathetic nervous system (SNS) activity. (ACTH) or cortisol-producing tumor effectively lowers
Increases in SNS output would be expected to raise blood pressure. The most effective antihypertensive
blood pressure through increases in cardiac output pharmacological agent in Cushing’s syndrome is a

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