scholarly journals Genetic and Adverse Health Outcome Associations with Treatment Resistant Hypertension in GenHAT

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Amy I. Lynch ◽  
Marguerite R. Irvin ◽  
Barry R. Davis ◽  
Charles E. Ford ◽  
John H. Eckfeldt ◽  
...  
Keyword(s):  
Resistant Hypertension ◽  
Genetic Variants ◽  
Antihypertensive Medication ◽  
Genetic Basis ◽  
Uncontrolled Hypertension ◽  
Treatment Resistant ◽  
Adverse Health Outcome ◽  
Genetic Studies ◽  
Similar Association ◽  
Agt Gene

Treatment resistant hypertension (TRH) is defined as uncontrolled hypertension (HTN) despite the use of ≥3 antihypertensive medication classes or controlled HTN while treated with ≥4 antihypertensive medication classes. Risk factors for TRH include increasing age, diminished kidney function, higher body mass index, diabetes, and African American (AA) race. Importantly, previous studies suggest a genetic role in TRH, although the genetics of TRH are largely understudied. With 2203 treatment resistant cases and 2354 treatment responsive controls (36% AA) from the Genetics of Hypertension Associated Treatment Study (GenHAT), we assessed the association of 78 candidate gene polymorphisms with TRH status using logistic regression. After stratifying by race and adjusting for potential confounders, there were 2 genetic variants in the AGT gene (rs699, rs5051) statistically significantly associated with TRH among white participants. The Met allele of rs699 and the G allele of rs5051 were positively associated with TRH:OR=1.27 (1.12–1.44),P=0.0001, andOR=1.36 (1.20–1.53),P<0.0001, respectively. There was no similar association among AA participants (race interactionP=0.0004for rs699 andP=0.0001for rs5051). This research contributes to our understanding of the genetic basis of TRH, and further genetic studies of TRH may help reach the goal of better clinical outcomes for hypertensive patients.

scholarly journals Adherence to Antihypertensive Medication in Treatment‐Resistant Hypertension Undergoing Renal Denervation

2016 ◽  
Vol 5 (2) ◽  
Author(s):  
Roland E. Schmieder ◽  
Christian Ott ◽  
Axel Schmid ◽  
Stefanie Friedrich ◽  
Iris Kistner ◽  
...  
Keyword(s):  
Resistant Hypertension ◽  
Antihypertensive Medication ◽  
Renal Denervation ◽  
Treatment Resistant

Abstract 094: Predicting the Risk of Apparent Treatment Resistant Hypertension: A Retrospective, Longitudinal, Cohort Study in an Urban Hypertension Referral Clinic Setting

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Michael G Buhnerkempe ◽  
Albert Botchway ◽  
Carlos Nolasco-Morales ◽  
Vivek Prakash ◽  
Lowell Hedquist ◽  
...  
Keyword(s):  
Negative Predictive Value ◽  
Risk Score ◽  
Resistant Hypertension ◽  
Predictive Value ◽  
Low Risk ◽  
Uncontrolled Hypertension ◽  
Treatment Resistant ◽  
Index Visit ◽  
Drug Classes

Background: Apparent treatment resistant hypertension (aTRH) is associated with increased prevalence of secondary hypertension and adverse pressure-related clinical outcomes. We previously showed that cross-sectional prevalence estimates of aTRH are lower than its true prevalence as patients with uncontrolled hypertension undergoing intensification/optimization of therapy will, over time, increasingly satisfy diagnostic criteria for aTRH. Methods: aTRH (SBP and/or DBP at or above a clinically defined goal BP [140/90, 130/85, 130/80, or 125/75 mmHg] over two consecutive office visits when on ≥ 3 antihypertensive drug classes, including a diuretic; or SBP and DBP below goal when on ≥ 4 drug classes, including a diuretic) was assessed in an urban referral hypertension clinic in 924 patients ≥ 30 years old (57.7 ± 12.6) with at least two follow-up visits over 240 days. Patients were mostly African-American (86%; 795/924) and female (65%; 601/924). A minority (28.7%; 265/924) were taking diuretics at their index visit, and analyses were stratified according to this use. Risk for aTRH was estimated using logistic regression with patient characteristics at index visit as predictors. Performance of this risk score at discriminating aTRH status over follow-up was assessed using AUC and was internally validated using bootstrapping. Results: Amongst those on diuretics, 80/265 (30.2%) developed aTRH; the risk score discriminated well (AUC = 0.79, bootstrapped 95% CI [0.73, 0.84]). In patients not on a diuretic, 151/659 (22.9%) developed aTRH, and the risk score showed moderate, but significantly lower, discriminative ability (AUC = 0.71 [0.66, 0.74]; p < 0.001). In the diuretic and non-diuretic cohorts, 43/265 (16.2%) and 101/265 (38.1%) of patients, respectively, had estimated risks for development of aTRH < 10%. Of these low-risk patients, 42/43 (97.7%) and 97/101 (96.0%) did not develop aTRH (negative predictive value, diuretics – 0.95 [0.93, 1.00], no diuretics – 0.96 [0.91, 1.00]). Conclusions: We created a novel clinical score that discriminates well between those who will and will not develop aTRH, especially amongst those taking diuretics initially. Irrespective of diuretic treatment status, a low risk score had very high negative predictive value.

scholarly journals Underutilization of Treatment for Black Adults With Apparent Treatment-Resistant Hypertension

Hypertension ◽  
2020 ◽  
Vol 76 (5) ◽  
pp. 1600-1607
Author(s):  
Aisha T. Langford ◽  
Oluwasegun P. Akinyelure ◽  
Tony L. Moore ◽  
George Howard ◽  
Yuan-I Min ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Resistant Hypertension ◽  
Mineralocorticoid Receptor ◽  
Antihypertensive Medication ◽  
Healthy Lifestyle ◽  
Lifestyle Factors ◽  
Mineralocorticoid Receptor Antagonists ◽  
Treatment Resistant ◽  
Black Adults

Resistant hypertension, defined as blood pressure levels above goal while taking ≥3 classes of antihypertensive medication or ≥4 classes regardless of blood pressure level, is associated with increased cardiovascular disease risk. The 2018 American Heart Association Scientific Statement on Resistant Hypertension recommends healthy lifestyle habits and thiazide-like diuretics and mineralocorticoid receptor antagonists for adults with resistant hypertension. The term apparent treatment-resistant hypertension (aTRH) is used when pseudoresistance cannot be excluded. We estimated the use of healthy lifestyle factors and recommended antihypertensive medication classes among US Black adults with aTRH. Data were pooled for Black participants in the JHS (Jackson Heart Study) in 2009 to 2013 (n=2496) and the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) in 2013 to 2016 (n=3786). Outcomes included lifestyle factors (not smoking, not consuming alcohol, ≥75 minutes of vigorous-intensity or ≥150 minutes of moderate or vigorous physical activity per week, and body mass index <25 kg/m 2 ) and recommended antihypertensive medications (thiazide-like diuretics and mineralocorticoid receptor antagonists). Overall, 28.3% of participants who reported taking antihypertensive medication had aTRH. Among participants with aTRH, 14.5% and 1.2% had ideal levels of 3 and 4 of the lifestyle factors, respectively. Also, 5.9% of participants with aTRH reported taking a thiazide-like diuretic, and 9.8% reported taking a mineralocorticoid receptor antagonist. In conclusion, evidence-based lifestyle factors and recommended pharmacological treatment are underutilized in Black adults with aTRH. Increased use of lifestyle recommendations and antihypertensive medication classes specifically recommended for aTRH may improve blood pressure control and reduce cardiovascular disease–related morbidity and mortality among US Black adults. Graphic Abstract A graphic abstract is available for this article.

scholarly journals Nonadherence in Hypertension: How to Develop and Implement Chemical Adherence Testing

Hypertension ◽  
2021 ◽  
Author(s):  
Dan Lane ◽  
Alexander Lawson ◽  
Angela Burns ◽  
Michel Azizi ◽  
Michel Burnier ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Resistant Hypertension ◽  
Antihypertensive Medication ◽  
Antihypertensive Drugs ◽  
Test Results ◽  
Sample Collection ◽  
Treatment Resistant ◽  
Blood Samples ◽  
Hypertensive Patients ◽  
Adherence Test

Nonadherence to antihypertensive medication is common, especially in those with apparent treatment-resistant hypertension (true treatment-resistant hypertension requires exclusion of nonadherence), and its routine detection is supported by clinical guidelines. Chemical adherence testing is a reliable and valid method to detect adherence, yet methods are unstandardized and are not ubiquitous. This article describes the principles of chemical adherence testing for hypertensive patients and provides a set of recommendations for centers wishing to develop the test. We recommend testing should be done in either of two instances: (1) in those who have resistant hypertension or (2) in those on 2 antihypertensives who have a less than 10 mm Hg drop in systolic blood pressure on addition of the second antihypertensive medication. Furthermore, we recommend that verbal consent is secured before undertaking the test, and the results should be discussed with the patient. Based on medications prescribed in United Kingdom, European Union, and United States, we list top 20 to 24 drugs that cover >95% of hypertension prescriptions which may be included in the testing panel. Information required to identify these medications on mass spectrometry platforms is likewise provided. We discuss issues related to ethics, sample collection, transport, stability, urine versus blood samples, qualitative versus quantitative testing, pharmacokinetics, instrumentation, validation, quality assurance, and gaps in knowledge. We consider how to best present, interpret, and discuss chemical adherence test results with the patient. In summary, this guidance should help clinicians and their laboratories in the development of chemical adherence testing of prescribed antihypertensive drugs.

scholarly journals Cardiovascular Health and Transition From Controlled Blood Pressure to Apparent Treatment Resistant Hypertension

Hypertension ◽  
2020 ◽  
Vol 76 (6) ◽  
pp. 1953-1961
Author(s):  
Oluwasegun P. Akinyelure ◽  
Swati Sakhuja ◽  
Calvin L. Colvin ◽  
Donald Clark ◽  
Byron C. Jaeger ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Racial Differences ◽  
Resistant Hypertension ◽  
Antihypertensive Medication ◽  
Cardiovascular Health ◽  
Treatment Resistant ◽  
Stroke Study ◽  
Life’S Simple 7 ◽  
Life's Simple 7

Almost 1 in 5 US adults with hypertension has apparent treatment resistant hypertension (aTRH). Identifying modifiable risk factors for incident aTRH may guide interventions to reduce the need for additional antihypertensive medication. We evaluated the association between cardiovascular health and incident aTRH among participants with hypertension and controlled blood pressure (BP) at baseline in the Jackson Heart Study (N=800) and the Reasons for Geographic and Racial Differences in Stroke study (N=2316). Body mass index, smoking, physical activity, diet, BP, cholesterol and glucose, categorized as ideal, intermediate, or poor according to the American Heart Association’s Life’s Simple 7 were assessed at baseline and used to define cardiovascular health. Incident aTRH was defined by uncontrolled BP, systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg, while taking ≥3 classes of antihypertensive medication or controlled BP, systolic BP <130 mm Hg and diastolic BP <80 mm Hg, while taking ≥4 classes of antihypertensive medication at a follow-up visit. Over a median 9 years of follow-up, 605 (19.4%) participants developed aTRH. Incident aTRH developed among 25.8%, 18.2%, and 15.7% of participants with 0 to 1, 2, and 3 to 5 ideal Life’s Simple 7 components, respectively. No participants had 6 or 7 ideal Life’s Simple 7 components at baseline. The multivariable adjusted hazard ratios (95% CIs) for incident aTRH associated with 2 and 3 to 5 versus 0 to 1 ideal components were 0.75 (0.61–0.92) and 0.67 (0.54–0.82), respectively. These findings suggest optimizing cardiovascular health may reduce the pill burden and high cardiovascular risk associated with aTRH among individuals with hypertension.

scholarly journals The Prevalence of Nonadherence in Patients With Resistant Hypertension: A Systematic Review Protocol

2019 ◽  
Vol 6 ◽  
pp. 205435811989719
Author(s):  
Gabrielle Bourque ◽  
Julius Vladimir Ilin ◽  
Marcel Ruzicka ◽  
Alexandra (Sascha) Davis ◽  
Swapnil Hiremath
Keyword(s):  
Systematic Review ◽  
Publication Bias ◽  
Resistant Hypertension ◽  
Observational Studies ◽  
Antihypertensive Medication ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Current Evidence ◽  
Treatment Resistant ◽  
Medication Nonadherence

Background: Resistant hypertension, usually defined as blood pressure remaining above goal despite the concurrent use of 3 or more antihypertensive agents of different classes, is common (about 10% prevalence) and known to be a risk factor for cardiovascular events. These patients also undergo more screening intensity for secondary hypertension. However, not all patients with apparent treatment-resistant hypertension have true resistant hypertension, with some of them being nonadherent to prescribed pharmacotherapy. The prevalence of nonadherence varies from about 5% to 80% in the published literature. However, the relative contributions of intentional and nonintentional nonadherence are not well described. Nonintentional nonadherence refers to occasional forgetfulness and/or carelessness and can sometimes be related to an inability to follow instructions, because of either cognitive or physical limitations. Intentional nonadherence refers to an active process in which a patient may choose to alter the prescribed medication regimen by discontinuing medications, skipping doses, or modifying doses or dosing intervals. Objective: Our objective is to establish the overall prevalence of nonadherence in the apparent treatment-resistant hypertension population and evaluate the relative contributions of nonintentional and intentional nonadherence subtypes. Design: We will conduct a systematic review and meta-analysis. Setting: We will include observational studies and randomized controlled trials where adherence to antihypertensive medications is measured using a test of adherence, either direct or indirect. Patients: We will include adult human participants aged 18 years or older with a diagnosis of resistant hypertension. Measurements: Data extracted from individual studies will include title, first author, design, country, publication year, funding body, method of assessing adherence to antihypertensive medication, prevalence of medication nonadherence, definition of resistant hypertension, sample size, sex, mean age, and coexistent comorbidities. Methods: A librarian will search the databases Medline, EMBASE, Cochrane, CINAHL, and Web of Science for studies meeting criteria for inclusion. Two reviewers will independently screen the titles and abstracts retrieved and assess the methodological quality of eligible full-text articles using the Cochrane Risk of Bias tool for clinical trials and the Newcastle-Ottawa Scale for observational studies. Summary estimates of prevalence will be generated using pooled analysis using the random-effects method. Subgroup analyses, sensitivity analyses, and evaluation of publication bias will also be performed. Results: The outcomes of interest are the pooled prevalence of nonadherence to antihypertensive medication in apparent treatment-resistant hypertension and the prevalence of nonadherence based on different methods of assessing nonadherence (indirect vs direct), which will allow us to estimate the relative proportion of unintentional and intentional nonadherence subtypes in the overall phenomenon of medication nonadherence. Limitations: Possible limitations of this study include the finding of severe heterogeneity, the limitations of the literature search, publication bias, and the lack of granular data in the published studies for a study-level meta-analysis. Conclusions: This systematic review will provide a synthesis of current evidence on the prevalence of medication nonadherence in apparent treatment-resistant hypertension and on the relative contributions of nonintentional and intentional nonadherence subtypes. These findings will provide clinicians with a better understanding of the factors underlying treatment-resistant hypertension and will serve as a strong research base to guide future research on interventions to address medication nonadherence as well as the nonintentional and intentional subtypes. Trial registration: This protocol has been registered with PROSPERO. We will add registration details once available.

Abstract P326: Apparent Treatment Resistant Hypertension and Risk for Stroke, Coronary Heart Disease and All-cause Mortality

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Marguerite R Irvin ◽  
John N Booth III ◽  
Daichi Shimbo ◽  
Daniel T Lackland ◽  
Suzanne Oparil ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Racial Differences ◽  
Resistant Hypertension ◽  
Antihypertensive Medication ◽  
Treatment Resistant ◽  
Hazard Ratios ◽  
All Cause Mortality ◽  
History Of

Apparent treatment resistant hypertension (aTRH) is characterized as uncontrolled hypertension (HTN) with the use of 3 or more antihypertensive medication classes or controlled HTN while treated with 4 or more antihypertensive medication classes. Few data are available on the association of aTRH with cardiovascular disease outcomes in comparison to more easily controlled HTN. We evaluated the risk for stroke, coronary heart disease (CHD) and all-cause mortality among 2,043 participants with aTRH and 9,519 participants with controlled HTN (systolic blood pressure < 140 mm Hg and diastolic blood pressure < 90 mm Hg) treated with < 4 antihypertensive medication classes from the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) study. aTRH was further categorized as controlled aTRH (≥ 4 antihypertensive medication classes and controlled HTN) and uncontrolled aTRH (≥ 3 antihypertensive medication classes and uncontrolled HTN). Participants with and without aTRH, respectively, were 68±9 and 66±9 years of age, 60.5% (1236 0f 2043) and 46.8% (4455 of 9519) black, and 49.2% (1005 of 2043) and 40.8% (3884 of 9519) male. After adjusting for demographic, clinical and comorbid factors, the hazard ratio (HR) for stroke, CHD, and all-cause mortality associated with aTRH (vs. controlled HTN and < 4 medication classes) was 1.29 (95% CI 0.96-1.73), 1.90 (95% CI 1.40-2.58), and 1.36 (95% CI 1.20-1.55), respectively. Compared to those with controlled hypertension, the multivariable-adjusted HR for stroke, CHD and all-cause mortality was increased for those with uncontrolled aTRH but not those with controlled aTRH (Table 1). Compared to those with controlled aTRH, uncontrolled aTRH was associated with CHD (HR 2.33; 95% CI: 1.21 [[Unable to Display Character: &#8211;]] 4.48) but not stroke (HR 1.05; 95% CI: 0.61 [[Unable to Display Character: &#8211;]] 1.81) or all-cause mortality (HR 1.15; 95% CI: 0.91 [[Unable to Display Character: &#8211;]] 1.45). We conclude achieving blood pressure control within aTRH is paramount to decrease risk for events similarly to other patients with more easily controlled HTN. Table 1. Hazard ratios for stroke, coronary heart disease, and all-cause mortality associated with apparent treatment resistant hypertension (aTRH). *< 4 antihypertensive medication classes Models are adjusted for age, race, gender, and geographic region of residence, waist circumference, smoking status, physical activity, alcohol consumption, C - reactive protein, statin use, Morisky score for medication adherence, total cholesterol, HDL-cholesterol, and hypertension duration, estimated glomerular filtration rate < 60 ml/min/1.73m 2 , albuminuria, and diabetes. Hazard ratios for stroke were also adjusted for history of coronary heart disease. Hazard ratios for coronary heart disease were also adjusted for history of stroke. Hazard ratios for all-cause mortality were also adjusted for history of coronary heart disease and stroke.

Abstract MP69: Prevalence of Treatment Resistant Hypertension Among Individuals with Chronic Kidney Disease: Results from the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Rikki M Tanner ◽  
David A Calhoun ◽  
Emmy K Bell ◽  
C. B Bowling ◽  
Orlando M Gutiérrez ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Racial Differences ◽  
Resistant Hypertension ◽  
Antihypertensive Medication ◽  
Treatment Resistant ◽  
High Prevalence ◽  
Regards Study ◽  
Multivariable Adjustment

Hypertension requiring treatment with multiple antihypertensive medications is common among individuals with chronic kidney disease (CKD). Small clinic-based studies have reported a high prevalence of treatment resistant hypertension (TRH) among patients with CKD. However, the prevalence of TRH has not been estimated for people with CKD in population-based studies. We hypothesized that lower estimated glomerular filtration rate (eGFR) and higher albumin-to-creatinine ratio (ACR) would be associated with a higher prevalence of TRH. We determined the prevalence of TRH among REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants (n=30,239) by eGFR and ACR and evaluated clinical and demographic correlates of TRH in those with CKD. Blood pressure was measured twice, pill bottles were inspected, and serum creatinine and an ACR were measured during an in-home study visit. TRH was defined as systolic/diastolic blood pressure ≥140/90 mmHg with concurrent use of ≥3 antihypertensive medication classes or use of ≥4 antihypertensive medication classes. CKD was defined as an ACR ≥30 mg/g or a CKD-EPI equation-derived eGFR <60 ml/min/1.73m 2 . The mean age of the 11,285 REGARDS participants treated for hypertension was 66.0 (SD=9.0) years, 56.9% were women and 48.8% were black. The prevalence of TRH was 14.5%, 23.5%, and 31.2% for those with an eGFR ≥60, 45-59, and <45 mL/min/1.73m 2 , respectively. The prevalence of TRH was 11.3%, 18.8%, 25.5%, and 44.5% for ACR <10, 10-29, 30-299, and ≥300 mg/g, respectively. A graded association between lower eGFR and higher ACR with TRH remained present after multivariable adjustment (Table 1). Also, after multivariable adjustment, black race, a larger waist circumference, diabetes, and history of myocardial infarction and stroke were associated with TRH among individuals with CKD. In conclusion, individuals with CKD have a high prevalence of TRH. Strategies are needed to improve blood pressure control in this population and reduce cardiovascular disease risk.

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