The possibility of resistant hypertension during the treatment of hypertensive patients

Nishikawa, Tetsuo; Omura, Masao; Saito, Jun; Matsuzawa, Yoko

doi:10.1038/hr.2013.107

Cited by 12 publications

(4 citation statements)

References 54 publications

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“…A Spanish registry [24] and a USA cross-sectional study [25] found around 12% of hypertensive patients met the criteria for RH. In Asian, the Japanese J-HOME study reported a prevalence of RH of 13% [26]. Our cohort showed a similar finding that 14.6% of the hypertensive patients in Taiwan met the definition of RH.…”

Section: Discussionsupporting

confidence: 85%

Resistant Hypertension, Patient Characteristics, and Risk of Stroke

Hung

Wang

et al. 2014

PLoS ONE

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BackgroundLittle is known about the prognosis of resistant hypertension (RH) in Asian population. This study aimed to evaluate the impacts of RH in Taiwanese patients with hypertension, and to ascertain whether patient characteristics influence the association of RH with adverse outcomes.Methods and ResultsPatients aged ≥45 years with hypertension were identified from the National Health Insurance Research Database. Medical records of 111,986 patients were reviewed in this study, and 16,402 (14.6%) patients were recognized as having RH (continuously concomitant use of ≥3 anti-hypertensive medications, including a diuretic, for ≥2 years). Risk of major adverse cardiovascular events (MACE, a composite of all-cause mortality, acute coronary syndrome, and stroke [included both fatal and nonfatal events]) in patients with RH and non-RH was analyzed. A total of 11,856 patients experienced MACE in the follow-up period (average 7.1±3.0 years). There was a higher proportion of females in the RH group, they were older than the non-RH (63.1 vs. 60.5 years) patients, and had a higher prevalence of cardiovascular co-morbidities. Overall, patients with RH had higher risks of MACE (adjusted HR 1.17; 95%CI 1.09–1.26; p<0.001). Significantly elevated risks of stroke (10,211 events; adjusted HR 1.17; 95%CI 1.08–1.27; p<0.001), especially ischemic stroke (6,235 events; adjusted HR 1.34; 95%CI 1.20–1.48; p<0.001), but not all-cause mortality (4,594 events; adjusted HR 1.06; 95%CI 0.95–1.19; p = 0.312) or acute coronary syndrome (2,145 events; adjusted HR 1.17; 95%CI 0.99–1.39; p = 0.070) were noted in patients with RH compared to those with non-RH. Subgroup analysis showed that RH increased the risks of stroke in female and elderly patients. However, no significant influence was noted in young or male patients.ConclusionsPatients with RH were associated with higher risks of MACE and stroke, especially ischemic stroke. The risks were greater in female and elderly patients than in male or young patients.

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Section: Discussionsupporting

confidence: 85%

Resistant Hypertension, Patient Characteristics, and Risk of Stroke

Hung

Wang

et al. 2014

PLoS ONE

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“…Oral contraceptive use was associated with greater GC sensitivity in response to a laboratory stressor in women (Rohleder et al, 2003), which could not be further explored in our study. In addition, as hypertension has been observed in hypercortisolemia (Nishikawa et al, 2013), BP is also a documented correlate with HPA dysregulation. Thus, certain demographic basic health characteristics should be considered in deciphering the depression-obesity-GC resistance.…”

Section: Discussionmentioning

confidence: 95%

Glucocorticoid mediated regulation of inflammation in human monocytes is associated with depressive mood and obesity

Cheng

Dimitrov

Pruitt

et al. 2016

Psychoneuroendocrinology

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Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is observed in various conditions, including depression and obesity, which are also often related. Glucocorticoid (GC) resistance and desensitization of peripheral GC receptors (GRs) are often the case in HPA dysregulation seen in depression, and GC plays a critical role in regulation of inflammation. Given the growing evidence that inflammation is a central feature of some depression cases and obesity, we aimed to investigate the immune-regulatory role of GC-GR in relation to depressive mood and obesity in 35 healthy men and women. Depressive mood and level of obesity were assessed, using Beck Depression Inventory (BDI-Ia) and body mass index (BMI), respectively. We measured plasma cortisol levels via enzyme-linked immunosorbent assay and lipopolysaccharide-stimulated intracellular tumor necrosis factor (TNF) production by monocytes, using flow cytometry. Cortisol sensitivity was determined by the difference in monocytic TNF production between the conditions of 1 and 0 μM cortisol incubation (“cortisol-mediated inflammation regulation, CoMIR”). GR vs. mineralocorticoid receptor (MR) antagonism for CoMIR was examined by using mifepristone and spironolactone. A series of multiple regression analyses were performed to investigate independent contribution of depressive mood vs. obesity after controlling for age, gender, systolic blood pressure (SBP), and plasma cortisol in predicting CoMIR. CoMIR was explained by somatic subcomponents of depressive mood (BDI-S: β= −0.499, p= 0.001), or BMI (β= −0.466, p< 0.01) in separate models. The effects of BMI disappeared when BDI-S was controlled for in the model, while BDI-S remained a significant independent predictor for CoMIR (β= −0.369, p< 0.05). However, BMI remained the only independent predictor when BDI-T or BDI-C were controlled for in the model. Mediation analyses also revealed that the relationship between BMI and CoMIR was mediated by BDI-S. The exploratory findings of the relative GR vs. MR roles in CoMIR, using GR and MR blockers, indicated that CoMIR in our cellular model was predominantly mediated by GRs at the higher cortisol dose (1 μM). There was initial indication that greater obesity and somatic depressive symptoms were associated with smaller efficacy of the blockers, which warrants further investigation. Our findings, although in a preclinical sample, signify the shared pathophysiology of immune dysregulation in depression and obesity and warrant further mechanistic investigation.

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“…2 Despite the use of generally effective antihypertensive therapy, blood pressure (BP) often remains above target levels because of poor adherence, an inadequate treatment regimen and/or treatment resistance. 3 Resistant hypertension is currently defined as the failure to achieve a goal of BPo140/90 mm Hg in patients who are compliant with the maximal tolerated doses of a minimum of three antihypertensive drugs, one of which is a diuretic. The prevalence of resistant hypertension is unknown, but clinical trials suggest that it is not rare and may involve perhaps 20-30% of the study participants.…”

Section: Introductionmentioning

confidence: 99%

Blood pressure decrease in spontaneously hypertensive rats folowing renal denervation or dopamine β-hydroxylase inhibition with etamicastat

et al. 2015

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Overactivity of the sympathetic nervous system has an important role in the development and progression of arterial hypertension. Catheter-based renal nerve ablation for the treatment of drug-resistant hypertension has recently been developed. An alternative strategy for the modulation of sympathetic nerve function is to reduce the biosynthesis of noradrenaline (NA) by inhibiting dopamine β-hydroxylase (DβH), the enzyme that catalyzes the conversion of dopamine (DA) to NA in the sympathetic nerves. Renal denervation (RDN) surgery was performed in spontaneously hypertensive rats (SHR) to evaluate the effect of RDN on the DA and NA levels and on blood pressure over a 28-day period. The selective peripheral DβH inhibitor etamicastat (30 mg kg (-1)day(-1)) was administered to another cohort of SHR. RDN and etamicastat treatment had no effect on the renal function, as assessed by measuring the water balance response, renal function and urinary electrolyte levels. RDN significantly decreased the systolic blood pressure (SBP) and the diastolic blood pressure (DBP). A gradual return of the SBP and the DBP to the high baseline levels was observed over time. Conversely, treatment with etamicastat resulted in a significant decrease in the SBP and the DBP at all time points. On the last day of the assessment, NA levels in renal tissue were significantly decreased in both RDN and etamicastat-treated groups. In contrast, the NA levels in the left ventricle were decreased only in the etamicastat-treated group. Thus, RDN produces transitory decreases in blood pressure, whereas prolonged downregulation of sympathetic drive with the DβH inhibitor etamicastat results in a sustained decrease in the SBP and the DBP.

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The possibility of resistant hypertension during the treatment of hypertensive patients

Cited by 12 publications

References 54 publications

Resistant Hypertension, Patient Characteristics, and Risk of Stroke

Resistant Hypertension, Patient Characteristics, and Risk of Stroke

Glucocorticoid mediated regulation of inflammation in human monocytes is associated with depressive mood and obesity

Blood pressure decrease in spontaneously hypertensive rats folowing renal denervation or dopamine β-hydroxylase inhibition with etamicastat

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