Clarifying the Cause and Treatment of Paroxysmal Hypertension (Pseudopheochromocytoma).

PURPOSE OF REVIEW: To review the clinical characteristics of paroxysmal hypertension (pseudopheochromocytoma), its previously unsuspected cause, and effective treatment approaches. RECENT FINDINGS: Patients with paroxysmal hypertension experience recurrent, sudden, unprovoked, symptomatic, and severe elevations of blood pressure that occur independently of current stress or perceived emotional distress. Recent findings point to a previously unsuspected psychosomatic etiology, linked in most to a past history of abuse, trauma, or prolonged severe stress, often with repression of pertinent emotions, or to a repressive coping style. Consistent with this understanding, treatment with an antidepressant is thus far the only pharmacologic intervention demonstrated to be effective in preventing recurrent paroxysms, and is effective in most patients. Other treatment approaches are discussed, including medications to acutely lower blood pressure during paroxysms, and, in some cases, the possibility of emotional healing.  Recent findings indicate that paroxysmal hypertension is a psychosomatic disorder frequently linked to a past history of trauma or prolonged severe stress, usually with longstanding repression of pertinent emotions. Data strongly encourage treatment with an antidepressant in patients with recurrent or severe paroxysms. Further studies are needed.

Neurogenic hypertension: pathophysiology, diagnosis and management.

Discussions about the cause and treatment of essential hypertension usually focus on mechanisms such as sodium/volume and the renin-angiotensin system. Less often discussed is hypertension driven by the sympathetic nervous system, i.e., neurogenic hypertension. In this review I discuss the pathophysiology of neurogenic hypertension, the controversy of renal versus central origin, the clinical clues that suggest neurogenic hypertension, and the interventions best suited in its treatment. Neurogenic hypertension is most likely to occur in patients with labile or paroxysmal hypertension, but evidence of increased sympathetic tone also suggests a neurogenic component in hypertension in patients with severe or resistant hypertension, chronic renal disease, comorbidities associated with increased sympathetic tone, and ingestion of drugs that stimulate sympathetic tone. The importance of combined alpha- and beta-blockade in pharmacologic treatment and the status of renal denervation are discussed. Although there is much that is unclear in its pathophysiology, recognition of neurogenic hypertension is of considerable clinical importance in individualizing drug therapy and achieving blood pressure control.

Loop Diuretics in the Treatment of Hypertension.

Loop diuretics are not recommended in current hypertension guidelines largely due to the lack of outcome data. Nevertheless, they have been shown to lower blood pressure and to offer potential advantages over thiazide-type diuretics. Torsemide offers advantages of longer duration of action and once daily dosing (vs. furosemide and bumetanide) and more reliable bioavailability (vs. furosemide). Studies show that the previously employed high doses of thiazide-type diuretics lower BP more than furosemide. Loop diuretics appear to have a preferable side effect profile (less hyponatremia, hypokalemia, and possibly less glucose intolerance). Studies comparing efficacy and side effect profiles of loop diuretics with the lower, currently widely prescribed, thiazide doses are needed. Research is needed to fill gaps in knowledge and common misconceptions about loop diuretic use in hypertension and to determine their rightful place in the antihypertensive arsenal.

Personalizing the diuretic treatment of hypertension: the need for more clinical and research attention.

Neither randomized controlled trials nor efforts to identify genetic markers have been helpful with regard to the goal of individualizing diuretic therapy in the treatment of hypertension, a goal that receives little clinical or research attention. This review will examine, and bring attention to, the considerable yet overlooked information relevant to individualizing diuretic therapy. It will bring attention to clinical, biochemical, and pharmacological clues that can be helpful in identifying who is likely to respond to a diuretic, who needs a stronger diuretic regimen, which diuretic to prescribe, and how to minimize adverse effects. New directions for clinical research aimed at individualizing use in hypertension will be explored. Research and clinical attention to the goal of individualizing diuretic treatment in hypertension need to be renewed, to help us achieve greater hypertension control with fewer adverse effects and lower costs.

Labile and Paroxysmal Hypertension: Common Clinical Dilemmas in Need of Treatment Studies.

Although "labile hypertension" is regularly encountered by clinicians, there is a paucity of information available to guide therapeutic decisions. This review discusses its clinical relevance, the limitations of current knowledge, and possible directions for future research and clinical management. Results of studies that assessed measures of blood pressure variability or reactivity are reviewed. The limited information about effects of antihypertensive drugs on blood pressure variability is discussed. Two different clinical presentations are differentiated: labile hypertension and paroxysmal hypertension. Labile hypertension remains a clinical impression without defined criteria or treatment guidance. Paroxysmal hypertension, also called pseudopheochromocytoma, presents as dramatic episodes of abrupt and severe blood pressure elevation. The disorder can be disabling. Although it regularly raises suspicion of a pheochromocytoma, such a tumor is found in <2 % of patients. The cause, which involves both emotional factors and the sympathetic nervous system, and treatment approaches, are presented.

High Dietary Sodium, Measured Using Spot Urine Samples, is Associated with Higher Blood Pressure among Young Adults in Haiti.

Background: Hypertension (HTN) is the leading cardiovascular disease (CVD) risk factor in Haiti and is likely driven by poverty-related social and dietary factors. Salt consumption in Haiti is hypothesized to be high but has never been rigorously quantified. Methods: We used spot urine samples from a subset of participants in the population-based Haiti Cardiovascular Disease Cohort to estimate population mean daily sodium intake. We compared three previously validated formulas for estimating dietary sodium intake using urine sodium, urine creatinine, age, sex, height, and weight. We explored the association between dietary sodium intake and blood pressure, stratified by age group. Results: A total of 1,240 participants had spot urine samples. Median age was 38 years (range 18-93), and 48% were female. The mean dietary sodium intake was 3.5-5.0 g/day across the three estimation methods, with 94.2%-97.9% of participants consuming above the World Health Organization (WHO) recommended maximum of 2 g/day of sodium. Among young adults aged 18-29, increasing salt intake from the lowest quartile of consumption (<3.73 g/day) to the highest quartile (>5.88 g/day) was associated with a mean 8.71 mmHg higher systolic blood pressure (SBP) (95% confidence interval: 3.35, 14.07; p = 0.001). An association was not seen in older age groups. Among participants under age 40, those with SBP ≥120 mmHg consumed 0.5 g/day more sodium than those with SBP <120 mmHg (95% confidence interval: 0.08, 0.69; p = 0.012). Conclusions: Nine out of 10 Haitian adults in our study population consumed more than the WHO recommended maximum for daily sodium intake. In young adults, higher sodium consumption was associated with higher SBP. This represents an inflection point for increased HTN risk early in the life course and points to dietary salt intake as a potential modifiable risk factor for primordial and primary CVD prevention in young adults.

Inaccuracy of self-reported low sodium diet.

OBJECTIVES: This study evaluates how often the self-report of a low sodium (Na) intake is reflected by a low 24-h urinary sodium excretion and examines the influence of incomplete urinary collections on this comparison. METHODS: In a study in which 24-h urine collections were obtained for measurement of Na and creatinine excretion, 120 participants were asked whether their Na intake was low, medium, or high. A 24-h urine collection was considered complete if creatinine excretion was ≥20 mg/kg in men or ≥15 mg/kg in women, and incomplete if below those amounts. The kappa statistic was computed to assess the level of agreement between 24-h Na excretion, dichotomized at 100 meq and self-report responses. RESULTS: Agreement between self-reported and actual Na excretion was poor. The kappa statistic was 0.18 for the total sample, 0.04 for complete collectors, and 0.51 for incomplete collectors, respectively. Overall, 24-h Na excretion exceeded 100 meq among 75% of those reporting an average or high Na intake, but it also exceeded 100 meq among 57% of those reporting a low sodium intake. Further, among those reporting a low sodium intake, Na excretion exceeded 100 meq in 80% of those who submitted a complete collection, but in only 29% of those who submitted an incomplete collection. CONCLUSIONS: These findings suggest that many individuals who report a low salt diet actually excrete ≥100 meq/day. Na intake is also frequently underestimated because many 24-h urine collections are incomplete.

Addressing the problem of inaccuracy of measured 24-hour urine collections due to incomplete collection.

The 24-hour urine collection is widely considered the gold standard for assessing 24-hour excretion of various analytes. Yet, studies show that >30% of collections are incomplete and hence understate the true 24-hour excretion. We previously validated an equation for estimating an individual's 24-hour creatinine excretion, based on weight, sex, race, and age. The present study examines whether routinely correcting measured 24-hour excretion of an analyte using the ratio of estimated to measured 24-hour urine creatinine mitigates the misleadingly low values that result from undercollection. Ninety-nine participants, recruited from an outpatient hypertension clinic, submitted a 24-hour urine collection for measurement of creatinine and sodium excretion. The urine collections were dichotomized into complete (n = 63) and incomplete (n = 36) collections based on previously described criteria for expected 24-hour creatinine excretion. To adjust for possible incompleteness of collections, the measured 24-hour values were then corrected by multiplying them by the ratio of estimated to measured 24-hour urine creatinine. The mean 24-hour creatinine excretion was 1682 mg/d among complete collectors. Among incomplete collectors, the mean was 1211 mg/d before and 1695 mg/d after, adjustment. Similarly, mean 24-hour sodium excretion was 156 mEq/d among complete collectors, whereas among incomplete collectors it was 121 mEq/d before and 171 mEq/d after, adjustment. Undercollection of 24-hour urines is a common problem and results in misleadingly low values for excretion of analytes being measured. Routine adjustment of 24-hour urine values using estimated values for 24-hour creatinine excretion can greatly mitigate artifactually low 24-hour excretion results.

Severe paroxysmal hypertension (pseudopheochromocytoma).

Paroxysmal hypertension always engenders a search for a catecholamine-secreting pheochromocytoma. Yet 98% of people with paroxysmal hypertension do not have this tumor. The cause and management of paroxysmal hypertension remain a mystery, and the subject of remarkably few papers. This review presents an approach to understanding and successfully treating this disorder. Patients experience symptomatic blood pressure surges likely linked to sympathetic nervous system stimulation. A specific personality profile associated with this disorder suggests a psychological basis, attributable to repressed emotion related to prior emotional trauma or a repressive (nonemotional) coping style. Based on this understanding, three forms of intervention, alone or in combination, appear successful: antihypertensive therapy with agents directed at the sympathetically mediated blood pressure elevation (eg, combined alpha- and beta-blockade or central alpha-agonists such as clonidine); psychopharmacologic interventions including anxiolytic and/or antidepressant agents; and psychological intervention, particularly reassurance and increased psychological awareness. An appropriately selected intervention can reduce or eliminate attacks in most patients.

The silent epidemic of thiazide-induced hyponatremia.

Hyponatremia is a recognized complication of treatment with thiazide diuretics, particularly in patients older than 70 years. Severe and symptomatic hyponatremia requires urgent management, usually requiring infusion of normal or hypertonic saline. Milder, asymptomatic, thiazide-induced hyponatremia requires steps to manage the hyponatremia as well as to prevent its future recurrence. This is a particular problem in patients who despite a history of thiazide-induced hyponatremia might require a diuretic in the management of their hypertension. In this review, the acute management of symptomatic and asymptomatic thiazide-induced hyponatremia is reviewed. Emphasis is also placed on the chronic management of patients who have experienced mild hyponatremia, in whom decisions about treatment with diuretic and nondiuretic antihypertensive agents must be made to satisfy the twin goals of controlling hypertension and avoiding recurrent hyponatremia.

Redefining beta-blocker use in hypertension: selecting the right beta-blocker and the right patient.

Randomized controlled trials have concluded that the cardiovascular outcome of first-step treatment of hypertension with traditional vasoconstricting beta-blockers is inferior to treatment with other antihypertensive drug classes. Beta-blocker use is also associated with undesirable side effects. Consequently, some recent guidelines consider beta-blockers an inferior option for first-step treatment of hypertension. Despite this, beta-blockers are still widely prescribed, and likely overused, in the management of hypertension. It is the contention of this perspective that beta-blockers do have an important role in treating hypertension, but their use needs to be much better targeted, by better identification of both the right patient and the right beta-blocker. Identifying the right patient involves consideration of underlying mechanisms of hypertension. In the absence of comorbidities for which a beta-blocker is indicated, beta-blockers would not seem to be the preferred treatment for patients with either sodium/volume-mediated hypertension, for which they are usually ineffective, or for those with renin-angiotensin system-mediated hypertension, for which angiotensin-converting enzyme inhibitors and angiotensin receptor blockers provide equal antihypertensive efficacy with evidence of better outcome and fewer adverse effects. Beta-blockers would instead appear to be best suited for patients with sympathetically driven, that is, neurogenic, hypertension, whether as a first-step drug, such as in patients with hypertension in the acute post-stroke period, in so-called "hyperkinetic" patients, and in patients with labile hypertension, or as an add-on drug in patients with resistant hypertension. In choosing among the beta-blockers, combined alpha/beta-blockade offers advantages over beta-blocker monotherapy and merits greater clinical and research attention. Finally, unreliable bioavailability greatly interferes with the effectiveness of lipophilic, but not nonlipophilic, beta-blockers. Clinical effectiveness could be improved with greater focus on the beta-blockers with the more favorable pharmacokinetics.

Nonadherence to Recommended Guidelines for Blood Pressure Measurement.

Accuracy of blood pressure readings, both in the physician's office and at home, is crucial in properly managing hypertension. Few studies have investigated adherence to measurement guidelines. This study focused on two important aspects of blood pressure measurement: waiting time before measurement and number of readings taken. A total of 103 patients completed self-report questionnaires about office and home blood pressure measurements, with 77% reporting that physician measurements were obtained without waiting, and 56% reporting that only one reading was obtained. The proportions were even higher when measured by a nurse/technician, 96% and 81%, respectively. Home readings were taken without waiting by 60%, and 40% reported taking only a single reading. Most patients received no measurement instructions. Nonadherence to measurement guidelines is common, and may be affecting the validity of readings obtained both in physicians' offices and at home, with significant and potentially harmful effects on treatment decisions.

Neurogenic essential hypertension revisited: the case for increased clinical and research attention.

The management of essential hypertension has increasingly focused on the use of diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers, which lower blood pressure (BP) through effects on blood volume and on the renin-angiotensin system. However, in many individuals these agents, whether given alone or in combination, fail to normalize BP. In such cases it is likely that hypertension is at least partly maintained by pathophysiologic mechanisms other than volume and the renin-angiotensin system, and therefore, that pharmacotherapy directed at other mechanisms is needed. One such form of hypertension is the often overlooked entity of neurogenic hypertension. The purpose of this article is to renew attention to this overlooked entity, to provide a very clinically oriented overview of its possible causes and manifestations, and to discuss the potentially important treatment implications of recognizing this form of hypertension. These implications underscore the need for further clinical and research attention concerning neurogenically mediated hypertension.

Psychological characteristics and responses to antihypertensive drug therapy.

The objective of this study was to explore the relationship between psychological characteristics and responses to antihypertensive drug therapy. Twenty-two hypertensive subjects underwent psychological evaluation and treatment with 1) a diuretic, hydrochlorothiazide (HCTZ); 2) an angiotensin-converting enzyme (ACE) inhibitor, quinapril; and 3) combined alpha + beta blockade (doxazosin + betaxolol). Anger-Out scores on the State-Trait Anger Expression Inventory were positively correlated with the HCTZ-induced fall in systolic blood pressure (p<0.01); Anger-In was negatively correlated with the quinapril-induced fall in systolic pressure (p<0.05). The target systolic blood pressure (130 mm Hg) was achieved with either HCTZ or quinapril in 79% of subjects without, vs. 25% of subjects with, childhood trauma (p=0.03). Responses to doxazosin + betaxolol were not correlated with psychological characteristics. The authors conclude that both inhibited anger expression and childhood trauma are associated with reduced response to a diuretic or ACE inhibitor. Combined alpha/beta blockade may be preferable to an ACE inhibitor or diuretic in treating selected hypertensive patients. Further studies should include examination of psychological factors in terms of the response to combined ACE inhibitor + diuretic therapy.

Development of a model to estimate 24-hour urinary creatinine excretion.

The accuracy of the spot urine analyte/creatinine ratio in estimating 24-hour excretion of the analyte is compromised because it is not adjusted for 24-hour creatinine excretion. The authors developed a model for conveniently estimating 24-hour creatinine excretion. The model was derived from 24-hour urine collections using multiple linear regression, including sex, weight, race, and age. The model was then evaluated in a validation cohort, assessing the correlation between estimated and measured 24-hour creatinine excretion and by comparing their correlation with muscle mass. Estimated creatinine excretion correlated strongly with measured creatinine excretion (r=0.80 in the entire cohort and 0.93 after eliminating patients with incomplete collections), and correlated at least as strongly as measured creatinine excretion with lean muscle mass (r=0.94 vs r=0.82, respectively). Adjusting spot urine analyte/creatinine ratios using the estimated 24-hour creatinine excretion by this convenient method can improve the accuracy of estimating 24-hour excretion of albumin, sodium, and other analytes.