Pharmacogenomics of Antihypertensive Drugs in Brazil: recent progress and clinical implications

2021 ◽  
Vol 22 ◽  
Author(s):  
Fabiana Dalla Vecchia Genvigir ◽  
Carolina Dagli Hernandez ◽  
Thiago Dominguez Crespo Hirata ◽  
Yitian Zhou ◽  
Volker M Lauschke ◽  
...  
Keyword(s):  
Genetic Factors ◽  
Antihypertensive Drugs ◽  
Gestational Hypertension ◽  
Pressure Control ◽  
Response To Therapy ◽  
Clinical Implications ◽  
Genetic Predictors ◽  
Antihypertensive Response ◽  
Drug Responsiveness ◽  
Multiple Drugs

Background: The available antihypertensive drugs are effective and well tolerated agents. However, only about half of patients with treated hypertension achieve appropriate blood pressure control. Genetic and non-genetic factors contribute to the interindividual variability of the therapeutic response Objective: This review constitutes a comprehensive update of the pharmacogenomics of antihypertensive drugs and their clinical implications in Brazil. Results: Twenty-five studies explored the influence of gene variants on drug response in patients with primary, resistant, or gestational hypertension. Variants in BDKRB2, NOS3, PRKCA, and VEGFA influenced the response to enalapril in patients with primary hypertension. AGT and MMP2 variants were associated with high risk of resistance to antihypertensive treatment, whereas NOS2 variants were related to low risk. Moreover, NAT2 slow acetylators showed an increased response to hydralazine in patients with resistant hypertension. HMOX1, NAMPT, MMP9, NOS3 and TIMP1 variants might be markers of drug responsiveness in hypertensive or preeclamptic pregnant women. Power and replication of studies, polygenic nature of response to therapy, and treatment with multiple drugs were important challenges to be overcome for identifying genetic predictors of antihypertensive response in Brazil. Conclusion: Pharmacogenomic studies in Brazilian cohorts provide some evidences of variants, mainly in pharmacodynamics genes, which influence the response to antihypertensive drugs. However, some findings are limited by cohort size or therapeutic scheme and may be influenced by interactions with other genetic and non-genetic factors. Therefore, further investigations are needed to elucidate the contribution of pharmacogenomics to the efficacy and safety of antihypertensive therapy.

scholarly journals Genetic predictors of participation in optional components of UK Biobank

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jessica Tyrrell ◽  
Jie Zheng ◽  
Robin Beaumont ◽  
Kathryn Hinton ◽  
Tom G. Richardson ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Genetic Variants ◽  
Genetic Factors ◽  
Mendelian Randomization ◽  
Genetic Correlations ◽  
Mr Studies ◽  
Uk Biobank ◽  
Factors Affecting ◽  
Participation Bias ◽  
Genetic Predictors

AbstractLarge studies such as UK Biobank are increasingly used for GWAS and Mendelian randomization (MR) studies. However, selection into and dropout from studies may bias genetic and phenotypic associations. We examine genetic factors affecting participation in four optional components in up to 451,306 UK Biobank participants. We used GWAS to identify genetic variants associated with participation, MR to estimate effects of phenotypes on participation, and genetic correlations to compare participation bias across different studies. 32 variants were associated with participation in one of the optional components (P < 6 × 10−9), including loci with links to intelligence and Alzheimer’s disease. Genetic correlations demonstrated that participation bias was common across studies. MR showed that longer educational duration, older menarche and taller stature increased participation, whilst higher levels of adiposity, dyslipidaemia, neuroticism, Alzheimer’s and schizophrenia reduced participation. Our effect estimates can be used for sensitivity analysis to account for selective participation biases in genetic or non-genetic analyses.

scholarly journals Improvement of Blood Pressure Control by Adherence Check in Patients With Apparent Treatment-Resistant Hypertension: A Case Series

2020 ◽  
Vol 13 ◽  
pp. 117954762090488
Author(s):  
Keiko Hosohata ◽  
Ayaka Inada ◽  
Saki Oyama ◽  
Takashi Doi ◽  
Iku Niinomi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Resistant Hypertension ◽  
Antihypertensive Drugs ◽  
Case Series ◽  
Pressure Control ◽  
Supporting Evidence ◽  
Treatment Resistant ◽  
Uncontrolled Blood Pressure ◽  
Important Challenge ◽  
Prescribed Medicines

Adherence to medications is an important challenge while treating chronic disease such as resistant hypertension, which is defined as uncontrolled blood pressure (BP) despite treatment with more than 3 antihypertensive drugs to achieve targets. It is possible that poor adherence is the most significant contributor to rates of pseudo-resistance among treated hypertensive patients. In this report, we describe 4 patients with apparent treatment-resistant hypertension, who received intervention to promote adherence by pharmacists who set the prescribed medicines in a weekly medication calendar and conducted a weekly pill count. The results showed that the intervention of pharmacists to medication adherence improved systolic BP in patients with apparent treatment-resistant hypertension; however, further controlled trials are required to strengthen supporting evidence.

scholarly journals Prediction of short-term antidepressant response using probabilistic graphical models with replication across multiple drugs and treatment settings

2021 ◽  
Author(s):  
Arjun P. Athreya ◽  
Tanja Brückl ◽  
Elisabeth B. Binder ◽  
A. John Rush ◽  
Joanna Biernacka ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Graphical Models ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Probabilistic Graphical Models ◽  
Sociodemographic Factors ◽  
Response To Therapy ◽  
Antidepressant Response ◽  
Symptom Profiles ◽  
Poor Outcomes ◽  
Multiple Drugs

AbstractHeterogeneity in the clinical presentation of major depressive disorder and response to antidepressants limits clinicians’ ability to accurately predict a specific patient’s eventual response to therapy. Validated depressive symptom profiles may be an important tool for identifying poor outcomes early in the course of treatment. To derive these symptom profiles, we first examined data from 947 depressed subjects treated with selective serotonin reuptake inhibitors (SSRIs) to delineate the heterogeneity of antidepressant response using probabilistic graphical models (PGMs). We then used unsupervised machine learning to identify specific depressive symptoms and thresholds of improvement that were predictive of antidepressant response by 4 weeks for a patient to achieve remission, response, or nonresponse by 8 weeks. Four depressive symptoms (depressed mood, guilt feelings and delusion, work and activities and psychic anxiety) and specific thresholds of change in each at 4 weeks predicted eventual outcome at 8 weeks to SSRI therapy with an average accuracy of 77% (p = 5.5E-08). The same four symptoms and prognostic thresholds derived from patients treated with SSRIs correctly predicted outcomes in 72% (p = 1.25E-05) of 1996 patients treated with other antidepressants in both inpatient and outpatient settings in independent publicly-available datasets. These predictive accuracies were higher than the accuracy of 53% for predicting SSRI response achieved using approaches that (i) incorporated only baseline clinical and sociodemographic factors, or (ii) used 4-week nonresponse status to predict likely outcomes at 8 weeks. The present findings suggest that PGMs providing interpretable predictions have the potential to enhance clinical treatment of depression and reduce the time burden associated with trials of ineffective antidepressants. Prospective trials examining this approach are forthcoming.

scholarly journals Blood Pressure Control: Stroke and Stroke Prevention

2005 ◽  
Vol 6 (1_suppl) ◽  
pp. S8-S11
Author(s):  
Hans-Christoph Diener
Keyword(s):  
Blood Pressure ◽  
Stroke Prevention ◽  
Antihypertensive Drugs ◽  
Angiotensin Receptor Blockers ◽  
Antihypertensive Agents ◽  
Pressure Control ◽  
Angiotensin Receptor ◽  
Risk Of Death ◽  
Pressure Lowering ◽  
Receptor Blockers

Hypertension is the most important modifiable risk factor for primary and secondary stroke prevention. All antihypertensive drugs are effective in primary prevention: the risk reduction for stroke is 30—42%. However, not all classes of drugs have the same effects: there is some indication that angiotensin receptor blockers may be superior to other classes of antihypertensive drugs in stroke prevention. Seventy-five percent of patients who present to hospital with acute stroke have elevated blood pressure within the first 24—48 hours. Extremes of systolic blood pressure (SBP) increase the risk of death or dependency. The aim of treatment should be to achieve and maintain the SBP in the range 140—160 mmHg. However, fast and drastic blood pressure lowering can have adverse consequences. The PROGRESS trial of secondary prevention with perindopril + indapamide versus placebo + placebo showed a decrease in numbers of stroke recurrences in patients given both active antihypertensive agents, more impressive for cerebral haemorrhage.There were also indications that active treatment might decrease the development of post-stroke dementia.

Effect of strict blood pressure control on proteinuria in renal patients treated with different antihypertensive drugs

2001 ◽  
Vol 16 (suppl_1) ◽  
pp. 78-81 ◽  
Author(s):  
Soledad García de Vinuesa ◽  
José Luño ◽  
Francisco Gómez‐Campderá ◽  
Natalia Ridao ◽  
Mercedes Sánchez ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Control ◽  
Antihypertensive Drugs ◽  
Pressure Control

scholarly journals Resistant Hypertension: A Real Entity Requiring Special Treatment?

2016 ◽  
Vol 11 (1) ◽  
pp. 8
Author(s):  
Stefano Taddei ◽  
Rosa Maria Bruno ◽  
◽  
◽  
Keyword(s):  
Blood Pressure ◽  
Resistant Hypertension ◽  
Renal Denervation ◽  
Antihypertensive Drugs ◽  
Pressure Control ◽  
Clinical Situation ◽  
Special Treatment ◽  
Separate Clinical Entity ◽  
Real Entity ◽  
Definition Of

Resistant hypertension (RH) was defined many years ago as a clinical situation in which blood pressure remains uncontrolled despite concomitant intake of at least three antihypertensive drugs (one of them preferably being a diuretic) at full doses. This operative definition was aimed at identifying a subset of hypertensive patients requiring a more extensive clinical workup in order to achieve an adequate blood pressure control. An oversimplification of this picture led to consider RH as a separate clinical entity requiring special, expensive treatments, such as renal denervation and baroreceptor activating therapy. In this review we will discuss the utility and the shortcomings of the definition of RH and the possible consequences for treatment.

scholarly journals Drug utilization study of antihypertensive drugs and prevalence of blood pressure control in adult hypertensive patients based on JNC VIII guidelines in a tertiary care hospital: a cross sectional study

2019 ◽  
Vol 8 (2) ◽  
pp. 245
Author(s):  
Saumya Ramadas ◽  
M. B. Sujatha ◽  
M. A. Andrews ◽  
Sanalkumar K. B.
Keyword(s):  
Blood Pressure ◽  
Combination Therapy ◽  
Drug Utilization ◽  
Antihypertensive Drug ◽  
Blood Pressure Control ◽  
Antihypertensive Drugs ◽  
Pressure Control ◽  
Antihypertensive Drug Therapy ◽  
Care Hospital ◽  
Drug Utilization Study

Background: Hypertension is a major independent risk factor for coronary artery disease, congestive heart failure, stroke, chronic kidney disease and peripheral vascular diseases if left untreated. Drug utilization study of antihypertensive drugs and the study on prevalence of blood pressure control would help in reducing the burden of the disease and health expenditure.Methods: The study was conducted in the Outpatient Department of Medicine in Government Medical College, Thrissur. Patients aged 18yrs or above diagnosed with hypertension, on antihypertensive drugs were enrolled in the study. Patients suffering from secondary hypertension and acutely ill were excluded. Patients were enrolled after taking an informed consent. Demographic data, present treatment for hypertension, associated co- morbid conditions if any, and treatment of the same were recorded. BP was recorded, and cost of treatment was calculated using CIMS.Results: A total of 250 patients were included in the study. Mono therapy was used in 64.8% patients and combination therapy in 35.2%. Overall drug utilization pattern showed that CCBs (42.8%) were most commonly prescribed, followed by ACEIs (32.4%) and ARBs (29.2%). Most commonly prescribed combination therapy was ACE I + BB (29.3%), followed by ARB + CCB (21.3%). Mean cost of antihypertensive drug therapy was 3057.8 Rs / yr. Recommended target BP was achieved in 49.6% of patients.Conclusions: The prescription pattern of antihypertensive drug was in accordance to the JNC-VIII guidelines. The blood pressure target was achieved only in less than 50% of patients.

scholarly journals Circulating Tumor Cells in Gastrointestinal Malignancies: Current Techniques and Clinical Implications

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Georg Lurje ◽  
Marc Schiesser ◽  
Andreas Claudius Hoffmann ◽  
Paul Magnus Schneider
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Disease Progression ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Response To Therapy ◽  
Clinical Implications ◽  
Gastrointestinal Malignancies ◽  
Progression Of Disease

Since their introduction more than 50 years by Engell, circulating tumor cells (CTCs) have been evaluated in cancer patients and their detection has been correlated with clinical outcome, in esophageal, gastric, and colorectal cancer. With the availability of refined technologies, the identification of CTCs from peripheral blood is emerging as a useful tool for the detection of malignancy, monitoring disease progression, and measuring response to therapy. However, increasing evidence suggests a variety of factors to be responsible for disease progression. The analysis of a single CTC marker is therefore unlikely to accurately predict progression of disease with sufficient resolution and reproducibility. Here we discuss the current concept of CTCs, summarize the available techniques for their detection and characterization, and aim to provide a comprehensive update on the clinical implications of CTCs in gastrointestinal (GI) malignancies.

scholarly journals Fetal Outcome in Hypertensive Disorders of Pregnancy.

2013 ◽  
Vol 12 (1) ◽  
pp. 8-10 ◽  
Author(s):  
Arju Chand Singh ◽  
Sadikchya Singh Rana
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Antihypertensive Drugs ◽  
Gestational Hypertension ◽  
Fetal Outcome ◽  
Intrauterine Fetal Death ◽  
Hypertensive Disorders Of Pregnancy ◽  
Hypertensive Disorders ◽  
Study Results ◽  
Low Birth Weight Babies

Introduction: Hypertensive disorders are the most common medical complications of pregnancy, affecting approximately 5-10% of pregnancies and the major cause of maternal and infant disease and death worldwide. Very few researches have been done in Nepal to analyze the effect of hypertension in fetus. The aim of this study was to determine the incidence and perinatal morbidity of hypertensive disorders of pregnancy. Methods: This was a hospital based prospective observational study conducted at Paropakar Maternity and Women’s hospital. The study was conducted from 18th October to 22nd December 2007. All primi and multigravid patient with BP ≥140/90 mmHg after 28 weeks of pregnancy were included in the study. Women with a blood pressure ≥140/90mmHg at or before 20 weeks of gestation, previous hypertension or women on antihypertensive drugs and Intrauterine fetal death (IUFD) were excluded from the study. Results: A total of 126 cases of hypertensive disorders of pregnancy were identifi ed among 3819 obstetric cases. The incidence of hypertensive disorders of pregnancy was 3.3%. Among 100 cases who were included in the study, 42 had pre eclampsia and 58 had gestational hypertension. Among 42 preeclamptic patients, 15(35.71%) had low birth weight babies, and 9(15.5%) babies had low birth weight among 58 gestational hypertensive mothers. Conclusions: Preeclampsia increases the risk of intrauterine growth restriction, low birth weight and stillbirth.Medical Journal of Shree Birendra Hospital; January-June 2013/vol.12/Issue1/8-10DOI:http://dx.doi.org/10.3126/mjsbh.v12i1.9083  

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