Mohammed Siddiqui

Resistant and Refractory Hypertension: Antihypertensive Treatment Resistance vs Treatment Failure.

Resistant or difficult to treat hypertension is defined as high blood pressure that remains uncontrolled with 3 or more different antihypertensive medications, including a diuretic. Recent definitions also include controlled blood pressure with use of 4 or more medications as also being resistant to treatment. Recently, refractory hypertension, an extreme phenotype of antihypertensive treatment failure has been defined as hypertension uncontrolled with use of 5 or more antihypertensive agents, including a long-acting thiazide diuretic and a mineralocorticoid receptor antagonist. Patients with resistant vs refractory hypertension share similar characteristics and comorbidities, including obesity, African American race, female sex, diabetes, coronary heart disease, chronic kidney disease, and obstructive sleep apnea. Patients with refractory vs resistant hypertension tend to be younger and are more likely to have been diagnosed with congestive heart failure. Refractory hypertension might also differ from resistant hypertension in terms of underlying cause. Preliminary evidence suggests that refractory hypertension is more likely to be neurogenic in etiology (ie, heightened sympathetic tone), vs a volume-dependent hypertension that is more characteristic of resistant hypertension in general.

Refractory Hypertension: A Novel Phenotype of Antihypertensive Treatment Failure

The term resistant hypertension has been used since the early 1960s to identify patients with difficult-to-treat hypertension, meaning mostly, resistance to pharmacological therapy.1 In the 5 decades since the term was seemingly first applied, resistant hypertension has been consistently defined as failure to control high blood pressure despite of use of ≥3 antihypertensive agents of different classes, including a diuretic.2–5 The 2008 American Heart Association Scientific Statement on resistant hypertension included in its definition patients whose blood pressure had been uncontrolled with 3 medications, but controlled with ≥4 medications.4 Although the number of medications required to satisfy the definition is arbitrary, the purpose of creating a category of resistant hypertension is to identify patients who, because of the difficulty in controlling their blood pressure, may benefit from special diagnostic and therapeutic considerations, including referral to a hypertension specialist. Having an agreed on definition that can be reliably applied to different cohorts has also facilitated research for this subgroup of patients, including identification of risk factors and underlying mechanisms, assessing outcomes and developing targeted treatments. The term refractory hypertension has often been used interchangeably with resistant hypertension to also refer to patients with difficult-to-treat hypertension.1–3,5 However, based on the number of respective PubMed citations resistant hypertension has been used much more often than refractory hypertension to indicate patients with hypertension resistant to pharmacological treatment. Recently, the term refractory hypertension has been applied to a small group of patients who are truly refractory to treatment, that is, patients who fail to achieve target blood pressure on maximal antihypertensive therapy.6 Determining whether such patients simply represent extreme cases of resistant hypertension or a novel phenotype in terms of risk and cause has been the focus of initial attempts to define and characterize …

Refractory versus resistant hypertension.

Purpose of review Refractory hypertension is a recently proposed phenotype of antihypertensive treatment failure. As such it represents an extreme subtype of resistant or difficult-to-treat hypertension. Resistant hypertension is relatively common with an estimated prevalence of 10–20% of treated hypertensive patients. It is typically defined as having an uncontrolled blood pressure on three or more antihypertensive medications, including a diuretic. Refractory hypertension is rare with a prevalence of approximately 5% of patients with uncontrolled resistant hypertension. It is defined as an uncontrolled blood pressure with the use of five or more antihypertensive medications, including a long-acting thiazide diuretic, such as chlorthalidone, and a mineralocorticoid receptor antagonist such as spironolactone. Recent findings Persistent excess fluid retention is thought to commonly underlie development of resistant hypertension, recent studies suggest that refractory may be more likely attributable to heightened sympathetic output as opposed to inappropriate fluid retention. Summary Treatment recommendations for resistant hypertension are generally based on intensification of diuretic therapy, especially with combined use of chlorthalidone and spironolactone. Although fuller elucidation is needed, such an approach may not be appropriate for refractory hypertension, which instead, may require effective sympathetic inhibition, either with medications or device-based approaches.

A survey of primary care resident attitudes toward continuity clinic patient handover

Background Transfer of clinic patients from graduating residents to interns or junior residents occurs every year, affecting large numbers of patients. Breaches in care continuity may occur, with potential for risk to patient safety. Several guidelines have been developed for implementing standardized inpatient sign-outs, but no specific guidelines exist for outpatient handover. Methods Residents in primary care programs – internal medicine, family medicine, and pediatrics – at a US academic medical center were invited to participate in an online survey. The invitation was extended approximately 2 years after electronic medical record (EMR) rollout began at the institution. Results Of 71 eligible residents, 22 (31%) responded to the survey. Of these, 18 felt that handover of ambulatory patients was at least moderately important – but only one affirmed the existence of a system for handover. IM residents perceived that they had the highest proportion of high-risk patients (p=0.042); transition-of-care letters were more important to IM residents than other respondents (p=0.041). Conclusion There is room for improvement in resident acknowledgement of handover processes in continuity clinics. In this study, IM residents attached greater importance to a specific handover tool than other primary care residents. Thus, the different primary care specialties may need to have different handover tools available to them within a shared EMR system.

White-Coat Effect Is Uncommon in Patients With Refractory HypertensionNovelty and Significance

Refractory hypertension is a recently described phenotype of antihypertensive treatment failure defined as uncontrolled blood pressure (BP) despite the use of ≥5 different antihypertensive agents, including chlorthalidone and spironolactone. Recent studies indicate that refractory hypertension is uncommon, with a prevalence of ≈5% to 10% of patients referred to a hypertension specialty clinic for uncontrolled hypertension. The prevalence of white-coat effect, that is, uncontrolled automated office BP ≥135/85 mm Hg and controlled out-of-office BP <135/85 mm Hg, by awake ambulatory BP monitor in hypertensive patients overall is ≈30% to 40%. The prevalence of white-coat effect among patients with refractory hypertension has not been previously reported. In this prospective evaluation, consecutive patients referred to the University of Alabama at Birmingham Hypertension Clinic for uncontrolled hypertension were enrolled. Refractory hypertension was defined as uncontrolled automated office BP ≥135/85 mm Hg with the use of ≥5 antihypertensive agents, including chlorthalidone and spironolactone. Automated office BP measurements were based on 6 serial readings, done automatically with the use of a BpTRU device unobserved in the clinic. Out-of-office BP measurements were done by 24-hour ambulatory BP monitor. Thirty-four patients were diagnosed with refractory hypertension, of whom 31 had adequate ambulatory BP monitor readings. White-coat effect was present in only 2 patients, or 6.5% of the 31 patients with refractory hypertension, suggesting that white-coat effect is largely absent in patients with refractory hypertension. These findings suggest that white-coat effect is not a common cause of apparent lack of BP control in patients failing maximal antihypertensive treatment.

Refractory Hypertension Is not Attributable to Intravascular Fluid Retention as Determined by Intracardiac VolumesNovelty and Significance

Refractory hypertension (RfHTN) is an extreme phenotype of antihypertensive treatment failure defined as lack of blood pressure control with ≥5 medications, including a long-acting thiazide and a mineralocorticoid receptor antagonist. RfHTN is a subgroup of resistant hypertension (RHTN), which is defined as blood pressure >135/85 mm Hg with ≥3 antihypertensive medications, including a diuretic. RHTN is generally attributed to persistent intravascular fluid retention. It is unknown whether alternative mechanisms are operative in RfHTN. Our objective was to determine whether RfHTN is characterized by persistent fluid retention, indexed by greater intracardiac volumes determined by cardiac magnetic resonance when compared with controlled RHTN patients. Consecutive patients evaluated in our institution with RfHTN and controlled RHTN were prospectively enrolled. Exclusion criteria included advanced chronic kidney disease and masked or white coat hypertension. All enrolled patients underwent biochemical testing and cardiac magnetic resonance. The RfHTN group (n=24) was younger (mean age, 51.7±8.9 versus 60.6±11.5 years; P=0.003) and had a greater proportion of women (75.0% versus 43%; P=0.02) compared with the controlled RHTN group (n=30). RfHTN patients had a greater left ventricular mass index (88.3±35.0 versus 54.6±12.5 g/m2; P<0.001), posterior wall thickness (10.1±3.1 versus 7.7±1.5 mm; P=0.001), and septal wall thickness (14.5±3.8 versus 10.0±2.2 mm; P<0.001). There was no difference in B-type natriuretic peptide levels and left atrial or ventricular volumes. Diastolic dysfunction was noted in RfHTN. Our findings demonstrate greater left ventricular hypertrophy without chamber enlargement in RfHTN, suggesting that antihypertensive treatment failure is not attributable to intravascular volume retention.

Case of Refractory Hypertension Controlled After Aortic and Mitral Valve Replacement and Coronary Artery Bypass Grafting

A 78-year-old black man presented to the Hypertension Clinic at the University of Alabama at Birmingham for uncontrolled blood pressure (BP). His BP remained uncontrolled (automated office, ≥135/85 mm Hg) from August 2011 to August 2016 in spite of use of 6 antihypertensive agents in adequate doses (Figure 1). During this time period, his average systolic BP was 167.1 mm Hg and average diastolic BP was 68.7 mm Hg. Figure 1. Blood pressure (BP) and antihypertensive medications before and after surgery. CABG indicates coronary artery bypass grafting. The patient was on 3 antihypertensive medications on initial presentation to University of Alabama at Birmingham in 2011, including an angiotensin receptor blocker (irbesartan), a calcium channel blocker (amlodipine), and a long-acting thiazide-like diuretic (chlorthalidone). Spironolactone was added as a fourth antihypertensive agent. Eventually, hydralazine—a vasodilator—and clonidine—a centrally acting sympatholytic—were added as the fifth and sixth antihypertensive agents. The patient’s BP remained uncontrolled on 6 different classes of antihypertensive medications (Figure 1). Comorbidities and secondary causes of hypertension were evaluated by biochemical analysis and imaging. ### Biochemical Analysis The patient was diagnosed with mild chronic kidney disease. Mean serum creatinine was 1.35 mg/dL with an estimated glomerular filtration rate of 58 mL/min per 1.73 m2. Diabetes mellitus was excluded (HbA1c was 5.5%), primary aldosteronism was excluded as the plasma aldosterone–renin ratio was <30 (plasma aldosterone was <4 ng/dL, and plasma renin activity was 1.0 ng/mL per hour), and pheochromocytoma …