Assessment of adherence to treatment in patients with resistant hypertension using toxicological serum analysis. A subgroup evaluation of the RESIST-POL study.

INTRODUCTION: Nonadherence to antihypertensive therapy is one of the main causes of resistant hypertension. OBJECTIVES: The aim of our study was to evaluate adherence to therapy in patients with resistant hypertension by determining serum antihypertensive drug levels with the use of liquid chromatography-tandem mass spectrometry (LC-MS/MS). PATIENTS AND METHODS: The study included 36 patients with primary resistant hypertension selected from the RESIST-POL study (23 men and 13 women; mean age, 52.5 ±9.1 years; range, 22-67 years; mean number of antihypertensive drugs, 5.3 ±1.4), who met all 3 inclusion criteria: use of ≥4 antihypertensive drugs; average daytime ambulatory systolic blood pressure ≥140 mmHg; one of the clinical features suggesting nonadherence. All patients had their serum drug levels assessed using LC-MS/MS. Patients in whom the serum level of at least 1 drug was below the limit of quantification for the method used were regarded as nonadherent. RESULTS: Of all study patients, nonadherence was observed in 31 patients (86.1%), and none of the prescribed drugs was detected (complete nonadherence) in 5 patients (13.9%). In 26 patients (72.2%), at least 1 of the prescribed drugs could not be detected (partial nonadherence). CONCLUSIONS: In our study, we documented a surprisingly low adherence to antihypertensive treatment in patients with resistant hypertension. Our results suggest that, particularly in those patients, the analysis of serum antihypertensive drug levels using LC-MS/MS might allow to avoid a comprehensive and costly diagnostic work-up including biochemical and imaging studies.

Measurements of plasma metanephrines by immunoassay vs liquid chromatography with tandem mass spectrometry for diagnosis of pheochromocytoma.

BACKGROUND: Reports conflict concerning measurements of plasma metanephrines (MNs) for diagnosis of pheochromocytomas/paragangliomas (PPGLs) by immunoassays compared with other methods. We aimed to compare the performance of a commercially available enzyme-linked immunoassay (EIA) kit with liquid chromatography-tandem mass spectrometric (LC-MS/MS) measurements of MNs to diagnose PPGLs. METHODS: In a substudy of a prospective, multicenter trial to study the biochemical profiles of monoamine-producing tumors, we included 341 patients (174 males and 167 females) with suspected PPGLs (median age 54 years), of whom 54 had confirmed PPGLs. Plasma MNs were measured by EIA and LC-MS/MS, each in a specialized laboratory. RESULTS: Plasma normetanephrine (NMN) and MN were measured 60 and 39% lower by EIA than by LC-MS/MS. Using upper cut-offs stipulated for the EIA, diagnostic sensitivity was only 74.1% at a specificity of 99.3%. In contrast, use of similar cut-offs for MN and overall lower age-adjusted cut-offs for NMN measured by LC-MS/MS returned a diagnostic sensitivity and specificity of 98.1 and 99.7%. Areas under receiver-operating characteristic curves, nevertheless, indicated comparable diagnostic performance of the EIA (0.993) and LC-MS/MS (0.985). Diagnostic sensitivity for the EIA increased to 96.2% with a minimal loss in specificity (95.1%) following use of cut-offs for the EIA adapted to correct for the negative bias. CONCLUSIONS: The EIA underestimates plasma MNs and diagnostic sensitivity is poor using commonly stipulated cut-offs, resulting in a high risk for missing patients with PPGLs. Correction of this shortcoming can be achieved by appropriately determined cut-offs resulting in comparable diagnostic performance of EIA and LC-MS/MS assays.

Factors associated with diastolic dysfunction in patients with resistant hypertension: resist-POL study.

BACKGROUND: Diastolic dysfunction has been shown to be an independent factor of cardiovascular diseases in patients with hypertension. Very often, obstructive sleep apnea (OSA) and metabolic syndrome (MS) coexist with resistant hypertension (RHTN) and may lead to diastolic dysfunction. Thus, the purpose of this study was to investigate whether OSA and MS are associated with diastolic dysfunction in patients with RHTN independently from other factors, including age, left ventricular mass index (LVMI), and blood pressure (BP). METHODS: Data from 155 patients (n = 92 men and 63 women) were analyzed. All patients underwent thorough examination, including biochemical evaluations, ambulatory blood pressure monitoring, polysomnography with assessment of apnea/hypopnea index (AHI), and echocardiography. LVMI and diastolic function parameters were obtained. RESULTS: Patients were divided into 2 groups based on the presence or absence of diastolic dysfunction: group 1 (E' < 10cm/second; n=87) and group 2 (E' > 10cm/second; n = 68). AHI, LVMI, and 24-hour systolic BP/diastolic BP values were higher in group 1. E' correlated with AHI (r = -0.25; P < 0.001), LVMI (r = -0.36; P < 0.0001), 24-h systolic BP/24-h diastolic BP (r = -0.28, P < 0.001; r = -0.30, P < 0.001, respectively), glucose level (r = -0.26; P < 0.01), and abdominal obesity (r = -0.28; P < 0.0001). In multivariable models decreased E' was independently related to the presence of MS or abdominal obesity when separate components of MS were included in the model. Age and 24-hour systolic BP were independently associated with decreased E'. However, the relationship of decreased E' with 24-hour systolic BP was nonsignificant if LVMI was included in the multivariable model. CONCLUSIONS: MS and abdominal obesity were independently associated with diastolic dysfunction in patients with RHTN. OSA was not confirmed to be an independent factor of diastolic dysfunction.