Blood pressure response to metoprolol and chlorthalidone in European and African Americans with hypertension

Mehanna, Mai; Gong, Yan; McDonough, Caitrin W.; Beitelshees, Amber L.; Gums, John G.; Chapman, Arlene B.; Schwartz, Gary L.; Turner, Stephen T.; Cooper‐DeHoff, Rhonda M.

doi:10.1111/jch.13094

Cited by 14 publications

(9 citation statements)

References 33 publications

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“…Afro-American) US patients [464], in contrast to the much scarcer database available for European black people, and thus we extrapolate from US data. However, this extrapolation requires some caution as differences between the North American and the European black population exist, especially with regard to socioeconomic status, cardiovascular risk [465,466], and the response to antihypertensive drug treatment [467]. BPrelated HMOD, as well as cardiovascular and renal complications, are more common and severe in black patients compared with age-matched white patients at any BP level [464].…”

Section: Hypertension In Different Ethnic Groupsmentioning

confidence: 99%

2018 ESC/ESH Guidelines for the management of arterial hypertension

Williams¹,

Mancia²,

Spiering³

et al. 2018

Journal of Hypertension

3,057

1,678

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Section: Hypertension In Different Ethnic Groupsmentioning

confidence: 99%

2018 ESC/ESH Guidelines for the management of arterial hypertension

Williams¹,

Mancia²,

Spiering³

et al. 2018

Journal of Hypertension

3,057

1,678

View full text Add to dashboard Cite

show abstract

“…The PEAR-2 and PEAR trials have been previously described in detail [ 45 , 46 ]. Briefly, PEAR-2 was a prospective, multicenter, open-label, sequential clinical trial (clinicaltrials.gov identifier: NCT01203852).…”

Section: Methodsmentioning

confidence: 99%

Metabolomics Signature of Plasma Renin Activity and Linkage with Blood Pressure Response to Beta Blockers and Thiazide Diuretics in Hypertensive European American Patients

et al. 2021

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Plasma renin activity (PRA) is a predictive biomarker of blood pressure (BP) response to antihypertensives in European–American hypertensive patients. We aimed to identify the metabolic signatures of baseline PRA and the linkages with BP response to β-blockers and thiazides. Using data from the Pharmacogenomic Evaluation of Antihypertensive Responses-2 (PEAR-2) trial, multivariable linear regression adjusting for age, sex and baseline systolic-BP (SBP) was performed on European–American individuals treated with metoprolol (n = 198) and chlorthalidone (n = 181), to test associations between 856 metabolites and baseline PRA. Metabolites with a false discovery rate (FDR) < 0.05 or p < 0.01 were tested for replication in 463 European–American individuals treated with atenolol or hydrochlorothiazide. Replicated metabolites were then tested for validation based on the directionality of association with BP response. Sixty-three metabolites were associated with baseline PRA, of which nine, including six lipids, were replicated. Of those replicated, two metabolites associated with higher baseline PRA were validated: caprate was associated with greater metoprolol SBP response (β = −1.7 ± 0.6, p = 0.006) and sphingosine-1-phosphate was associated with reduced hydrochlorothiazide SBP response (β = 7.6 ± 2.8, p = 0.007). These metabolites are clustered with metabolites involved in sphingolipid, phospholipid, and purine metabolic pathways. The identified metabolic signatures provide insights into the mechanisms underlying BP response.

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“…Although poor control of high blood pressure may have many causes, the most likely contributor is the poor response to the prescribed antihypertensive drug [ 10 ]. Current drugs are used to treat HTN without an in-depth understanding of the biological basis that regulates the disease or the effect of an individual’s make-up on the efficacy of the drug to control HTN [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Hypertension in African Populations: Review and Computational Insights

Mabhida

Mashatola

Kaur

et al. 2021

Genes

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Hypertension (HTN) is a persistent public health problem affecting approximately 1.3 billion individuals globally. Treatment-resistant hypertension (TRH) is defined as high blood pressure (BP) in a hypertensive patient that remains above goal despite use of ≥3 antihypertensive agents of different classes including a diuretic. Despite a plethora of treatment options available, only 31.0% of individuals have their HTN controlled. Interindividual genetic variability to drug response might explain this disappointing outcome because of genetic polymorphisms. Additionally, the poor knowledge of pathophysiological mechanisms underlying hypertensive disease and the long-term interaction of antihypertensive drugs with blood pressure control mechanisms further aggravates the problem. Furthermore, in Africa, there is a paucity of pharmacogenomic data on the treatment of resistant hypertension. Therefore, identification of genetic signals having the potential to predict the response of a drug for a given individual in an African population has been the subject of intensive investigation. In this review, we aim to systematically extract and discuss African evidence on the genetic variation, and pharmacogenomics towards the treatment of HTN. Furthermore, in silico methods are utilized to elucidate biological processes that will aid in identifying novel drug targets for the treatment of resistant hypertension in an African population. To provide an expanded view of genetic variants associated with the development of HTN, this study was performed using publicly available databases such as PubMed, Scopus, Web of Science, African Journal Online, PharmGKB searching for relevant papers between 1984 and 2020. A total of 2784 articles were reviewed, and only 42 studies were included following the inclusion criteria. Twenty studies reported associations with HTN and genes such as AGT (rs699), ACE (rs1799752), NOS3 (rs1799983), MTHFR (rs1801133), AGTR1 (rs5186), while twenty-two studies did not show any association within the African population. Thereafter, an in silico predictive approach was utilized to identify several genes including CLCNKB, CYPB11B2, SH2B2, STK9, and TBX5 which may act as potential drug targets because they are involved in pathways known to influence blood pressure. Next, co-expressed genes were identified as they are controlled by the same transcriptional regulatory program and may potentially be more effective as multiple drug targets in the treatment regimens for HTN. Genes belonging to the co-expressed gene cluster, ACE, AGT, AGTR1, AGTR2, and NOS3 as well as CSK and ADRG1 showed enrichment of G-protein-coupled receptor activity, the classical targets of drug discovery, which mediate cellular signaling processes. The latter is of importance, as the targeting of co-regulatory gene clusters will allow for the development of more effective HTN drug targets that could decrease the prevalence of both controlled and TRH.

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Blood pressure response to metoprolol and chlorthalidone in European and African Americans with hypertension

Cited by 14 publications

References 33 publications

2018 ESC/ESH Guidelines for the management of arterial hypertension

2018 ESC/ESH Guidelines for the management of arterial hypertension

Metabolomics Signature of Plasma Renin Activity and Linkage with Blood Pressure Response to Beta Blockers and Thiazide Diuretics in Hypertensive European American Patients

Hypertension in African Populations: Review and Computational Insights

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