Cardiovascular risk of systolic versus diastolic blood pressure in Western and non-Western countries.
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Adult↗
Biomedical subjects
Mari K Nishizaka
Publications and source records attributed to Mari K Nishizaka.
Primary aldosteronism: diagnostic and therapeutic considerations.
Recent evaluations indicate that primary aldosteronism (PA) is common in patients with hypertension. In patients with mild to moderate hypertension the prevalence of PA is 5% to 10%, whereas in subjects with resistant hypertension the prevalence is approximately 20%. As such, PA has become the most common secondary cause of hypertension. Such high prevalence rates are distinctly different from earlier assessments in which PA was found to be rare, with a prevalence of generally less than 1% of hypertensive patients. Why PA is seemingly so much more common now than when first described remains unknown. Accurate identification of PA allows for specific therapy with aldosterone antagonists or with surgical resection of aldosterone-producing adenomas. Determination of the plasma aldosterone to plasma renin activity ratio is an effective screen for PA in that it has a high negative predictive value even in the setting of ongoing antihypertensive therapy. Its specificity, however, is low such that a high ratio is suggestive of PA but must be confirmed by demonstration of high and autonomous secretion of aldosterone.
Adrenalectomy↗
Aldosterone antagonism: an emerging strategy for effective blood pressure lowering.
Aldosterone antagonists have been available for many decades for the treatment of hypertension, but their use has been mostly limited to patients with classic primary aldosteronism or to combination products with hydrochlorothiazide to minimize risk for hypokalemia. Recently, indications for aldosterone antagonists have been expanded to include congestive heart failure and first-line treatment of mild-to-moderate hypertension. In addition, we have reported that spironolactone has significant antihypertensive benefit when added to existing regimens in patients with resistant hypertension. This benefit was present in patients with and without hyperaldosteronism and was additive to chronic renin-angiotensin blockade with angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs). Eplerenone, a selective aldosterone antagonist, avoids the androgen and progesterone receptor-related adverse events that sometimes occur with spironolactone, such as breast tenderness, gynecomastia, sexual dysfunction, and menstrual irregularities. In clinical trials, eplerenone has been shown to have antihypertensive benefit in treating mild-to-moderate hypertension similar to other widely used classes of agents. With recent demonstrations of benefit in multiple segments of the hypertensive population, aldosterone antagonists represent emerging opportunity for controlling high blood pressure.
Eplerenone↗
The role of aldosterone antagonists in the management of resistant hypertension.
Resistant hypertension is an increasingly common problem faced by primary care physicians and specialists and will undoubtedly become even more common as the adult population ages and gains weight. In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), at least 8% of subjects were resistant to treatment based on the need for three or more antihypertensive agents. Characteristics of patients with resistant hypertension include being older, black, obese, and diabetic, and having chronic kidney disease as well as untreated sleep apnea. Hyperaldosteronism is common in patients with resistant hypertension, with a prevalence of approximately 20%. This, however, is likely an underestimation of the role aldosterone excess plays in causing drug resistance. In subjects with resistant hypertension, suppressed renin levels are common, exceeding 75% in our studies, suggesting aldosterone excess effects beyond cases of true primary hyperaldosteronism. Recent studies indicate that aldosterone antagonists provide significant blood pressure reduction when added to antihypertensive regimens of patients with resistant hypertension. Interestingly, the blood pressure reduction with use of spironolactone is not limited to patients with hyperaldosteronism, consistent with the concept of aldosterone excess as a continuum from low-renin hypertension with normal aldosterone levels to true primary hyperaldosteronism.
Drug Resistance↗
Validity of plasma aldosterone-to-renin activity ratio in African American and white subjects with resistant hypertension.
BACKGROUND: Recent reports suggesting that primary aldosteronism (PA) is more common than historically thought have often relied on use of the plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio (ARR) to identify patients with PA. Prior determinations of the validity of the ARR had been generally limited to subjects that could be withdrawn from antihypertensive therapy and to non-African American subjects. METHODS AND RESULTS: The current study was designed to evaluate prospectively the diagnostic value of the ARR in treated African American and white subjects with resistant hypertension. Consecutive subjects referred to a university hypertension clinic for resistant hypertension were evaluated with an early morning ARR and a 24-h urinary aldosterone and sodium. The presence of PA was defined as a suppressed PRA (<1.0 ng/mL/h) and elevated urinary aldosterone excretion (>12 microg/24 h) during high dietary sodium ingestion (>200 mEq/24 h). In 58 subjects, PA was confirmed. The ARR was elevated (>20) in 45 of 58 subjects with PA and in 35 of the 207 patients without PA, resulting in a sensitivity of 78% and specificity of 83% with a corresponding positive predictive value of 56% and a negative predictive value of 93%. Among African American subjects, the ARR was less sensitive than in white subjects (75% v 80%), but it still had a high negative predictive value (92% v 94%). CONCLUSIONS: These data indicate that the ARR is valid as a screening test for PA in African American and white patients on stable antihypertensive treatments, but a high percentage of false-positive results precludes using it for accurate diagnosis of PA.
Black or African American↗
Impaired endothelium-dependent flow-mediated vasodilation in hypertensive subjects with hyperaldosteronism.
BACKGROUND: Recent studies suggest that aldosterone may impair endothelium-dependent vascular function through suppression of nitric oxide formation. Assessments of forearm blood flow or arterial compliance suggest a similar effect in humans. The present study was designed to determine whether chronic aldosterone excess in subjects with resistant hypertension impairs endothelium-dependent vascular reactivity as indexed by direct assessment of brachial artery flow-mediated dilation (FMD). METHODS AND RESULTS: Consecutive subjects (n=80) with resistant hypertension were prospectively evaluated with an early-morning ratio of plasma aldosterone to plasma renin activity and 24-hour urinary aldosterone and sodium. Changes in brachial artery diameter during reactive hyperemia were measured by high-resolution ultrasound. Hyperaldosteronism was diagnosed on the basis of a renin activity <1.0 ng x mL(-1) x h(-1), urinary aldosterone >12 microg/24 h, and urinary sodium >200 mEq/24 h. FMD was significantly lower in 36 subjects with hyperaldosteronism (1.8+/-1.3% versus 3.9+/-1.9% from baseline; P<0.0001) compared with the 44 subjects without hyperaldosteronism. FMD was negatively and significantly correlated with plasma aldosterone (r=-0.38, P=0.0006), 24-hour urinary aldosterone (r=-0.49, P<0.0001), and ratio of plasma aldosterone to plasma renin activity (r=-0.43, P<0.0001) but was independent of blood pressure, age, and body mass index. In 30 subjects, 3 months of treatment with spironolactone significantly increased FMD (2.5+/-1.7 versus 6.0+/-2.0%; P<0.0001) independently of blood pressure change. CONCLUSIONS: These data demonstrate a strong association between aldosterone excess and impaired endothelial function in human subjects as indexed by flow-mediated arterial vasodilation. These results suggest that chronic aldosteronism may have a blood pressure-independent effect on cardiovascular disease progression in subjects with resistant hypertension.
Adult↗
Use of aldosterone antagonists in resistant hypertension.
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Clinical Trials as Topic↗
Aldosterone excretion among subjects with resistant hypertension and symptoms of sleep apnea.
OBJECTIVE: The severity of obstructive sleep apnea (OSA) correlates with the difficulty of controlling BP. The mechanism, however, by which sleep apnea contributes to the development of resistant hypertension remains obscure. Having observed a high prevalence of OSA among hypertensive subjects with primary hyperaldosteronism, we hypothesized a possible association between sleep apnea and aldosterone excretion. DESIGN: In consecutive subjects referred to a university clinic for resistant hypertension, we prospectively determined plasma renin activity (PRA), plasma aldosterone concentration (PAC), and 24-h urinary aldosterone excretion during high dietary salt ingestion. In addition, all subjects completed the Berlin Questionnaire, a survey designed to identify subjects at risk of having sleep apnea. Primary hyperaldosteronism (PA) was defined as a PRA < 1.0 ng/mL/h and 24-h urinary aldosterone excretion > 12 micro g during high urinary sodium excretion (> 200 mEq/24 h). RESULTS: Of the 114 subjects evaluated, 72 subjects had a high probability and 42 subjects had a low probability of having sleep apnea based on their responses to the Berlin Questionnaire. Subjects at high risk for sleep apnea were almost two times more likely to have PA diagnosed (36 vs 19%, p < 0.05), tended to have lower PRA (1.2 +/- 1.8 ng/mL/h vs 1.9 +/- 4.1 ng/mL/h), and had significantly greater 24-h urinary aldosterone excretion (13.6 +/- 9.6 micro g vs 9.8 +/- 7.6 micro g, p < 0.05) compared to subjects at low risk of sleep apnea. CONCLUSION: These data provide evidence of increased aldosterone excretion in subjects with resistant hypertension and symptoms of sleep apnea. While the causality of this association is unknown, it is hypothesized that sleep apnea contributes to the development of resistant hypertension by stimulating aldosterone excretion.
Aldosterone↗
Resistant hypertension.
Recent clinical trials suggest that resistant hypertension is increasingly common. In the majority of patients, uncontrolled hypertension is due to persistent elevation of the systolic blood pressure. Older age and obesity are associated with poor blood pressure control. Other contributing factors include severity of the underlying hypertension and renal insufficiency. Poor patient adherence is thought be a common cause of medication resistance. Exogenous substances such as nonsteroidal anti-inflammatory drugs, oral contraceptives, and sympathomimetic agents can interfere with treatment. The prevalence of secondary causes of hypertension increases with age, especially atherosclerotic renal artery stenosis. Recent reports suggest that primary aldosteronism may be the most common secondary cause of hypertension. It should be considered in all patients with resistant hypertension. Effective treatment of resistant hypertension requires identification and reversal of contributing factors and/or secondary causes of hypertension. Pharmacologic therapy should utilize combination therapy, including a long-acting diuretic.
Age Factors↗
Hyperaldosteronism among black and white subjects with resistant hypertension.
Recent reports suggesting that the prevalence of primary hyperaldosteronism may be higher than historically thought have relied on an elevated plasma aldosterone concentration/plasma renin activity ratio to either diagnose or identify subjects at high risk of having primary hyperaldosteronism and have not included suppression testing of all evaluated subjects. In this prospective study of 88 consecutive patients referred to a university clinic for resistant hypertension, we determined the 24-hour urinary aldosterone excretion during high dietary salt ingestion, baseline plasma renin activity, and plasma aldosterone in all subjects. Primary hyperaldosteronism was confirmed if plasma renin activity was <1.0 ng/mL per hour and urinary aldosterone was >12 microg/24-hour during high urinary sodium excretion (>200 mEq/24-hour). Eighteen subjects (20%) were confirmed to have primary hyperaldosteronism. The prevalence of hyperaldosteronism was similar in black and white subjects. Of the 14 subjects with confirmed hyperaldosteronism who have been treated with spironolactone, all have manifested a significant reduction in blood pressure. In this population, an elevated plasma aldosterone/plasma renin activity ratio (>20) had a sensitivity of 89% and a specificity of 71% with a corresponding positive predictive value of 44% and a negative predictive value of 96%. These data provide strong evidence that hyperaldosteronism is a common cause of resistant hypertension in black and white subjects. The accuracy of these results is strengthened by having done suppression testing of all evaluated subjects.
Adult↗