Genetics of Resistant Hypertension: a Novel Pharmacogenomics Phenotype

Rouby, Nihal El; Cooper‐DeHoff, Rhonda M.

doi:10.1007/s11906-015-0583-8

Cited by 15 publications

(14 citation statements)

References 94 publications

(94 reference statements)

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“…Finally, a major challenge in designing optimal studies to identify and characterize the genetic architecture of resistant hypertension may be related to the as-of-yet unknown etiology of the phenotype(s) [ 10 ]. For example, more traditional pharmacogenomics studies of blood pressure and response to anti-hypertensive treatments concentrate on a single class of drug (such as hydrochlorothiazide monotherapy [ 93 ]) representing a specific pathway or mechanism of action.…”

Section: Discussionmentioning

confidence: 99%

“…Along with age and obesity, well-established independent risk factors of resistant hypertension, several other lifestyle and biological risk factors are believed to contribute to resistant hypertension, including excess alcohol use, increased dietary sodium intake, and use of several classes of medications (such as non-steroidal anti-inflammatory drugs, corticosteroids, and calcineurin inhibitors) [ 9 ]. Genetic factors may also play a role [ 10 ]. Numerous genetic variants have been identified in studies of the genetic architecture of hypertension and variation in blood pressure [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Genome-wide study of resistant hypertension identified from electronic health records

et al. 2017

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Resistant hypertension is defined as high blood pressure that remains above treatment goals in spite of the concurrent use of three antihypertensive agents from different classes. Despite the important health consequences of resistant hypertension, few studies of resistant hypertension have been conducted. To perform a genome-wide association study for resistant hypertension, we defined and identified cases of resistant hypertension and hypertensives with treated, controlled hypertension among >47,500 adults residing in the US linked to electronic health records (EHRs) and genotyped as part of the electronic MEdical Records & GEnomics (eMERGE) Network. Electronic selection logic using billing codes, laboratory values, text queries, and medication records was used to identify resistant hypertension cases and controls at each site, and a total of 3,006 cases of resistant hypertension and 876 controlled hypertensives were identified among eMERGE Phase I and II sites. After imputation and quality control, a total of 2,530,150 SNPs were tested for an association among 2,830 multi-ethnic cases of resistant hypertension and 876 controlled hypertensives. No test of association was genome-wide significant in the full dataset or in the dataset limited to European American cases (n = 1,719) and controls (n = 708). The most significant finding was CLNK rs13144136 at p = 1.00x10-6 (odds ratio = 0.68; 95% CI = 0.58–0.80) in the full dataset with similar results in the European American only dataset. We also examined whether SNPs known to influence blood pressure or hypertension also influenced resistant hypertension. None was significant after correction for multiple testing. These data highlight both the difficulties and the potential utility of EHR-linked genomic data to study clinically-relevant traits such as resistant hypertension.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genome-wide study of resistant hypertension identified from electronic health records

et al. 2017

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“…Additional studies have cited a myriad of ENaC, mineralocorticoid receptor, and CYP enzyme variants that are common in patients with RH. However, in order to determine the clinical significance of such a vast number of variants more comprehensive research, such as genome-wide association study, is required [ 21 , 31 , 32 ].…”

Section: Definition Of Resistant Hypertensionmentioning

confidence: 99%

Renal Innervation in Resistant Hypertension: A Review of Pathophysiology and Renal Denervation as Potential Treatment

Wilson

Gandhi

Suh

et al. 2020

CHYR

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Background: Advances in treatment and increased awareness have improved the prognosis for many patients with hypertension (HTN). Resistant hypertension (RH) refers to a subset of hypertensive individuals who fail to achieve a desired blood pressure (BP) despite concurrent use of 3 different classes antihypertensive agents, one being a diuretic, and proper lifestyle changes. The prevalence and prognosis of RH are unclear owing to its heterogeneous etiologies, risk factors, and secondary comorbidities. Previous research has provided evidence that increased renal sympathetic nerve activity (RSNA) within the renal artery contributes to RH development. Renal denervation (RDN) is a procedure that attempts to ameliorate the effects of heightened RSNA via ablation renal sympathetic fibers. BP reductions associated with RDN may be attributed to decreased norepinephrine spillover, restoration of natriuresis, increasing renal blood flow, and lowering plasma renin activity. Early clinical trials perpetuated positive results, and enthusiasm grew exponentially. However, recent clinical trials have called into question RDN's efficacy. Numerous limitations must be addressed to discern the true effectiveness of RDN as a therapeutic option for RH. Objective: We aimed to review the current understanding of RH, the anatomy of renal arteries, physiology of RH on renal arteries, anatomical pathways of the sympathetic involved in RH, RDN as a treatment option, and all relevant clinical trials treating RH with RDN. Methods: We piloted a MEDLINE® database search of literature extending from 1980 to 2017, with emphasis on the previous five years, combining keywords such as "resistant hypertension" and "renal denervation." Conclusion: A plethora of information is available regarding heightened RSNA leading to RH. RDN as a possible treatment option has shown a range of results. Reconciling RDN's true efficacy requires future trials to increased sites of nerve ablation, standardized protocol, increased anatomical understanding per individual basis, stricter guidelines regarding study design, increased operator experience, and integrating the use of a multielectrode catheter.

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“…Studies have also investigated genetic associations with adverse metabolic effects, including new-onset diabetes; however, uncertainty exists as to whether these genetic signals are promising. Finally, a relatively new focus on the genetic predictors of resistant hypertension seems to hold promise, and could help to identify patients in whom an aggressive approach to treatment will be needed 32 .…”

Section: Hypertension Pharmacogenomicsmentioning

confidence: 99%

Hypertension pharmacogenomics: in search of personalized treatment approaches

Cooper‐DeHoff

Johnson

2015

Nat Rev Nephrol

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Cardiovascular and renal diseases are associated with many risk factors, of which hypertension is one of the most prevalent. Worldwide, blood pressure control is only achieved in ~50% of those treated for hypertension, despite the availability of a considerable number of antihypertensive drugs from different pharmacological classes. Although many reasons exist for poor blood pressure control, a likely contributor is the inability to predict to which antihypertensive drug an individual is most likely to respond. Hypertension pharmacogenomics and other ‘omics’ technologies have the potential to identify genetic signals that are predictive of response or adverse outcome to particular drugs, and guide selection of hypertension treatment for a given individual. Continued research in this field will enhance our understanding of how to maximally deploy the various antihypertensive drug classes to optimize blood pressure response at the individual level. This Review summarizes the available literature on the most convincing genetic signals associated with antihypertensive drug responses and adverse cardiovascular outcomes. Future research in this area will be facilitated by enhancing collaboration between research groups through consortia such as the International Consortium for Antihypertensives Pharmacogenomics Studies, with the goal of translating replicated findings into clinical implementation.

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Genetics of Resistant Hypertension: a Novel Pharmacogenomics Phenotype

Cited by 15 publications

References 94 publications

Genome-wide study of resistant hypertension identified from electronic health records

Genome-wide study of resistant hypertension identified from electronic health records

Renal Innervation in Resistant Hypertension: A Review of Pathophysiology and Renal Denervation as Potential Treatment

Hypertension pharmacogenomics: in search of personalized treatment approaches

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