Should Antihypertensive Treatment Recommendations Differ in Patients With and Without Coronary Heart Disease? (from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT]).

Thiazide-type diuretics have been recommended for initial treatment of hypertension in most patients, but should this recommendation differ for patients with and without coronary heart disease (CHD)? The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind hypertension treatment trial in 42,418 participants with high risk of combined cardiovascular disease (CVD) (25% with preexisting CHD). This post hoc analysis compares long-term major clinical outcomes in those assigned amlodipine (n = 9048) or lisinopril (n = 9,054) with those assigned chlorthalidone (n = 15,255), stratified by CHD status. After 4 to 8 years, randomized treatment was discontinued. Total follow-up (active treatment + passive surveillance using national databases for deaths and hospitalizations) was 8 to 13 years. For most CVD outcomes, end-stage renal disease, and total mortality, there were no differences across randomized treatment arms regardless of baseline CHD status. In-trial rates of CVD were significantly higher for lisinopril compared with chlorthalidone, and rates of heart failure were significantly higher for amlodipine compared with chlorthalidone in those with and without CHD (overall hazard ratios [HRs] 1.10, p <0.001, and 1.38, p <0.001, respectively). During extended follow-up, significant outcomes according to CHD status interactions (p = 0.012) were noted in amlodipine versus chlorthalidone comparison for CVD and CHD mortality (HR 0.88, p = 0.04, and 0.84, p = 0.04, respectively) in those with CHD at baseline (HR 1.06, p = 0.15, and 1.08, p = 0.17) and in those without. The results of the overall increased stroke mortality in lisinopril compared with chlorthalidone (HR 1.2; p = 0.03) and hospitalized heart failure in amlodipine compared with chlorthalidone (HR 1.12; p = 0.01) during extended follow-up did not differ by baseline CHD status. In conclusion, these results provide no reason to alter our previous recommendation to include a properly dosed diuretic (such as chlorthalidone 12.5 to 25 mg/day) in the initial antihypertensive regimen for most hypertensive patients.

Normal fractional urate excretion identifies hyponatremic patients with reset osmostat.

BACKGROUND: Reset osmostat (RO) occurs in 36% of patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH) and is not often considered when evaluating hyponatremic patients. Patients with RO are not usually treated, but recent awareness that symptoms are associated with mild hyponatremia creates a therapeutic dilemma. We encountered patients with hyponatremia, hypouricemia and high urine sodium concentration (UNa), who had normal fractional excretion (FE) of urate and excreted dilute urines that were consistent with RO. We decided to test whether a normal FEurate in nonedematous hyponatremia irrespective of UNa or serum urate would identify patients with RO. METHODS: We determined FEurate in nonedematous hyponatremic patients. A diagnosis of RO was made if urine osmolality (Uosm) was <200 mOsm/kg in a random urine. We performed a modified water-loading test in patients with a normal FEurate whose random Uosm was >200 mOsm/kg. RESULTS: All nonedematous hyponatremic patients with FEurate of 4%-11% had RO, as determined by Uosm <200 mOsm/kg on a random urine collection in 8 patients, or after a modified water-loading test in 6 patients. Plasma antidiuretic hormone (ADH) in 4 patients was undetectable at <1 pg/mL during water-loading. Nine patients had baseline concentrated urine, 12 had UNa >20 mmol/L, 9 were hypouricemic, yet all had a normal FEurate. Comorbidities were similar to those reported in RO. CONCLUSIONS: RO, a benign form of SIADH, occurs commonly. A normal FEurate in a nonedematous hyponatremic patient is highly suggestive of RO. Determining FEurate is superior to serum urate. The therapeutic dilemma for RO must be resolved.

Is it cerebral or renal salt wasting?

Cerebral salt-wasting (CSW), or renal salt-wasting (RSW), has evolved from a misrepresentation of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) to acceptance as a distinct entity. Challenges still confront us as we attempt to differentiate RSW from SIADH, ascertain the prevalence of RSW, and address reports of RSW occurring without cerebral disease. RSW is redefined as 'extracellular volume depletion due to a renal sodium transport abnormality with or without high urinary sodium concentration, presence of hyponatremia or cerebral disease with normal adrenal and thyroid function.' Our inability to differentiate RSW from SIADH lies in the clinical and laboratory similarities between the two syndromes and the difficulty of accurate assessment of extracellular volume. Radioisotopic determinations of extracellular volume in neurosurgical patients reveal renal that RSW is more common than SIADH. We review the persistence of hypouricemia and increased fractional excretion of urate in RSW as compared to correction of both in SIADH, the appropriateness of ADH secretion in RSW, and the importance of differentiating renal RSW from SIADH because of disparate treatment goals: fluid repletion in RSW and fluid restriction in SIADH. Patients with RSW are being incorrectly treated by fluid restriction, with clinical consequences. We conclude that RSW is common and occurs without cerebral disease, and propose changing CSW to RSW.

Lack of comparability of intact parathyroid hormone measurements among commercial assays for end-stage renal disease patients: implication for treatment decisions.

BACKGROUND: Variability among assays used to measure intact parathyroid hormone (iPTH) is of particular concern because of the routine use of iPTH assay results to guide management of osteodystrophy and calcium metabolism in patients with end-stage renal disease (ESRD). The aim of this study was to determine the extent to which results from commercially available iPTH assays diverge from results obtained with the Nichols Allegro(R) Intact PTH immunoradiometric assay (IRMA), which was used as evidence in the development of the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines. METHODS: We divided EDTA plasma from 46 dialysis patients with ESRD and measured iPTH values with the following commercially available iPTH assays: Nichols' Allegro iPTH IRMA, Nichols Advantage iPTH immunochemiluminescent assay (ICMA), Scantibodies' Total Intact PTH IRMA, DiaSorin's N-tact iPTH IRMA, DPC's Coat-A-Count iPTH IRMA, Roche's Elecsys iPTH ICMA, and DSL's Active iPTH IRMA. RESULTS: Method comparison showed considerable interassay differences in the measurement of iPTH in ESRD patients. IPTH values assessed by other methods ranged, on average, from 60% to 152% of the Nichols Allegro IRMA values. Of the 6 iPTH assays tested, only the Scantibodies Total Intact PT IRMA (P = 0.7554) and the Roche Elecsys iPTH ICMA (P = 0.1327) resulted in iPTH values not statistically different from those obtained with the Nichols Allegro iPTH IRMA. CONCLUSIONS: Noncomparability among iPTH assays remains a distinct problem for the management of ESRD patients. These results should be taken into consideration when determining the course of medical treatment based on measured iPTH concentrations.