Hypertension Control During the Coronavirus Disease 2019 Pandemic: A Cohort Study Among US Veterans.

DESIGN: Retrospective cohort study. OBJECTIVE: We sought to examine whether disruptions in follow-up intervals contributed to hypertension control. BACKGROUND: Disruptions in health care were widespread during the coronavirus disease 2019 pandemic. PATIENTS AND METHODS: We identified a cohort of individuals with hypertension in both prepandemic (March 2019-February 2020) and pandemic periods (March 2020-February 2022) in the Veterans Health Administration. First, we calculated follow-up intervals between the last prepandemic and first pandemic blood pressure measurement during a primary care clinic visit, and between measurements in the prepandemic period. Next, we estimated the association between the maintenance of (or achieving) hypertension control and the period using generalized estimating equations. We assessed associations between follow-up interval and control separately for periods. Finally, we evaluated the interaction between period and follow-up length. RESULTS: A total of 1,648,424 individuals met the study inclusion criteria. Among individuals with controlled hypertension, the likelihood of maintaining control was lower during the pandemic versus the prepandemic (relative risk: 0.93; 95% CI: 0.93, 0.93). Longer follow-up intervals were associated with a decreasing likelihood of maintaining controlled hypertension in both periods. Accounting for follow-up intervals, the likelihood of maintaining control was 2% lower during the pandemic versus the prepandemic. For uncontrolled hypertension, the likelihood of gaining control was modestly higher during the pandemic versus the prepandemic (relative risk: 1.01; 95% CI: 1.01, 1.01). The likelihood of gaining control decreased with follow-up length during the prepandemic but not pandemic. CONCLUSIONS: During the pandemic, longer follow-up between measurements contributed to the lower likelihood of maintaining control. Those with uncontrolled hypertension were modestly more likely to gain control in the pandemic.

Correlates of Spontaneous Blood Pressure Reduction Following Severe Inpatient Hypertension Development.

BACKGROUND: Severe hypertension (sHTN) is prevalent in 10% of hospitalized patients and treatment guidelines are lacking. As such, patients who develop sHTN might unnecessarily receive antihypertensive medications which could lead to worse outcomes. Our goal was to investigate correlates of spontaneous blood pressure (BP) reduction to help guide future treatment decisions and avoid harm associated with aggressive BP treatment. METHODS: This is a retrospective cohort study of hospitalized adults between 2016 and 2020 who developed sHTN, SBP >180 or DBP >110 mmHg, after admission. Spontaneous BP reduction was defined as a SBP <160 and a DBP <100 mmHg achieved within 3 hours of sHTN in the absence of antihypertensive therapy. Multivariable logistic regression was used to identify correlates of spontaneous BP reduction. RESULTS: Of the 12,825 patients who developed sHTN, 44.2% had spontaneous BP reduction. After adjustment, we found that patients most likely to experience a BP drop received steroids before onset of sHTN (Odds Ratio [OR]: 1.3 [1.09, 1.56]), had higher potassium levels on admission (OR: 1.2 [1.09, 1.24]) and were more likely to have a history of chronic pulmonary disease (OR: 1.1 [1.01, 1.18]) or cardiac arrythmia (OR: 1.1 [1.01, 1.18]). While numerically different, these differences were not clinically relevant. CONCLUSION: Our findings indicate that almost half the patients who develop sHTN have spontaneous BP reduction. Conventional clinical and demographic characteristics were not strong predictors of spontaneous BP reduction following sHTN development. More research is needed to confirm our findings and help guide treatment of sHTN.

Effect of intravenous antihypertensives on outcomes of severe hypertension in hospitalized patients without acute target organ damage.

BACKGROUND: Treatment of severe inpatient hypertension (HTN) that develops during hospitalization is not informed by guidelines. Intravenous (i.v.) antihypertensives are used to manage severe HTN even in the absence of acute target organ damage; however they may result in unpredictable blood pressure (BP) reduction and cardiovascular events. Our goal was to assess the association between i.v. antihypertensives and clinical outcomes in this population. METHODS: This is a multihospital retrospective study of adults admitted for reasons other than HTN who develop severe HTN during hospitalization without acute target end organ damage. We defined severe HTN as BP elevation of systolic >180 or diastolic >110 mmHg. Treatment was defined as receiving i.v. antihypertensives within 3 h of BP elevation. We used overlap propensity score weighted Cox models to study the association between treatment and clinical outcomes during index hospitalization. RESULTS: Of 224 265 unique, nonintensive care unit hospitalizations, 20 383 (9%) developed severe HTN, of which 5% received i.v. antihypertensives and 79% were untreated within 3 h of severe BP elevation. In the overlap propensity weighted population, patients who received i.v. antihypertensives were more likely to develop myocardial injury (5.9% in treated versus 3.6% in untreated; hazard ratio [HR]: 1.6 [1.13, 2.24]). Treatment was not associated with increased risk of stroke (HR: 0.7 [0.3, 1.62]), acute kidney injury (HR: 0.97 [0.81, 1.17]), or death (HR: 0.86 [0.49, 1.51]). CONCLUSIONS: Intravenous antihypertensives were associated with increased risk of myocardial injury in patients who develop severe HTN during hospitalization. These results suggest that i.v. antihypertensives should be used with caution in patients without acute target organ damage.

Neurogenic orthostatic hypotension after treatment with sorafenib.

A man in his 70s with a history of fatigue, abdominal pain, and a palpable abdominal mass was found to have a peritoneal desmoid tumour. One year after diagnosis, he was prescribed sorafenib to limit tumour growth. Two months later, he developed dyspnoea on exertion and lower extremity weakness and was reported to have supine hypertension and orthostatic hypotension. On formal autonomic testing, he was noted to have severely impaired sympathetic responses and marked orthostatic hypotension without appropriate chronotropic response. A decision to hold sorafenib was made, and treatment was started with graduated compression stockings, liberal fluid and sodium intake, and midodrine. The patient had a modest and gradual improvement in his symptoms. To our knowledge, this is the first reported case of orthostatic hypotension related to sorafenib or any vascular endothelial growth factor inhibitors.

Blood pressure response to commonly administered antihypertensives for severe inpatient hypertension.

BACKGROUND: Blood pressure (BP) elevations are commonly treated in hospitalized patients; however, treatment is not guideline directed. Our objective was to assess BP response to commonly prescribed antihypertensives after the development of severe inpatient hypertension (HTN). METHODS: This is a cohort study of adults, excluding intensive care unit patients, within a single healthcare system admitted for reasons other than HTN who developed severe HTN (systolic BP>180 or diastolic BP >110 mmHg at least 1 hour after admission). We identified the most commonly administered antihypertensives given within 6 hours of severe HTN (given to >10% of treated patients). We studied the association of treatment with each antihypertensive vs. no treatment on BP change in the 6 hours following severe HTN development using mixed-effects model after adjusting for demographics and clinical characteristics. RESULTS: Among 23,147 patients who developed severe HTN, 9,166 received antihypertensive treatment. The most common antihypertensives given were oral metoprolol (n = 1991), oral amlodipine (n = 1812), oral carvedilol (n = 1116), IV hydralazine (n = 1069) and oral hydralazine (n = 953). In the fully adjusted model, treatment with IV hydralazine led to 13 [-15.9, -10.1], 18 [-22.2, -14] and 11 [-14.1, -8.3] mmHg lower MAP, SBP, and DBP in the 6 hours following severe HTN development compared to no treatment. Treatment with oral hydralazine and oral carvedilol also resulted in significantly lower BPs in the 6 hours following severe HTN development (6 [-9.1, -2.1 and -7 [-9.1, -4.2] lower MAP, respectively) compared to no treatment. Receiving metoprolol and amlodipine did not result in a drop in BP compared to no treatment. CONCLUSION: Among commonly used antihypertensives, IV hydralazine resulted in the most significant drop in BP following severe HTN, while metoprolol and amlodipine did not lower BP. Further research to assess the effect of treatment on clinical outcomes and if needed which antihypertensives to administer are necessary.

Evaluation and management of orthostatic hypotension: Limited data, limitless opportunity.

Although orthostatic hypotension is common and can have serious consequences, recommendations about its evaluation and management are based on limited data. Here, the author outlines a systematic approach, noting the areas that pose an opportunity for improvement.

Excessive Blood Pressure Response to Clonidine in Hospitalized Patients With Asymptomatic Severe Hypertension.

BACKGROUND: There are limited and nonconcordant data on the rapidity and safety of blood pressure response to clonidine in the setting of asymptomatic severe hypertension. We evaluated the blood pressure response to clonidine in hospitalized patients with asymptomatic severe hypertension. METHODS: We performed a review of hospitalized, noncritically ill patients receiving clonidine within 6 hours of developing asymptomatic severe hypertension (systolic blood pressure [SBP] >180 or diastolic blood pressure [DBP] >110 mm Hg in the absence of acute hypertension-mediated target organ damage). The incidence of mean arterial pressure (MAP) reduction by ≥30% at 4 hours after clonidine was the primary endpoint. RESULTS: We identified 200 relevant patient encounters (median age 63 years, 48.5% women). Median time to clonidine following asymptomatic severe hypertension was 2.8 hours. A total of 20 (10%) patients had ≥30% MAP reduction within 4 hours after clonidine, and 32 (16%) patients had ≥30% reduction in either SBP, DBP, or MAP. Older age, female sex, and preexisting vascular disease were associated with ≥30% MAP reductions (P < 0.05). Only patient sex and clonidine dose of 0.3 mg were significant in multivariable models. There were 14 adverse events observed within 24 hours of administration of clonidine; most (9) were acute kidney injury. There were no ischemic (myocardial, cerebrovascular) events. CONCLUSIONS: A substantial minority of hospitalized patients with asymptomatic severe hypertension experience precipitous blood pressure decline with clonidine, and though blood pressure declines more precipitously in women and those receiving higher doses (0.3 mg specifically), the response to clonidine is generally not predictable on clinical grounds.

Seronegative autoimmune autonomic ganglionopathy from dual immune checkpoint inhibition in a patient with metastatic melanoma.

BACKGROUND: Immune checkpoint inhibitors have improved clinical outcomes including survival in several malignancies but have also been associated with a range of immune-related adverse events (irAEs). Neurological irAEs are rare compared to the more typical skin, gastrointestinal, and endocrine toxicities, and are often underrecognized and challenging to diagnose. Here, we report a case of seronegative autoimmune autonomic ganglionopathy (AAG) induced by dual immune checkpoint inhibitor therapy (ICI) in a patient with metastatic melanoma. CASE PRESENTATION: A patient with metastatic melanoma was treated with ipilimumab and nivolumab. He developed a constellation of new symptoms including nausea, fatigue, and severe orthostatic hypotension refractory to fluid resuscitation. An infectious, cardiac, neurologic, and endocrine workup were unrevealing. Cardiovascular autonomic testing revealed poor sympathetic nervous system responses. He was diagnosed with seronegative AAG and significantly improved with immunomodulatory therapies including IVIG and steroids as well as varying doses of midodrine and fludrocortisone. He was able to restart nivolumab without recurrence of his symptoms. However, the AAG reoccurred when he was re-challenged with ipilimumab and nivolumab due to disease progression. While the AAG was manageable with steroids at that time, unfortunately his melanoma became resistant to ICI. CONCLUSIONS: Immune checkpoint inhibitors can have a wide range of unusual, rare irAEs, including neurotoxicity such as AAG. Clinicians should maintain suspicion for this toxicity so that treatment can be rapidly provided to avoid disability.

A Survey of Patient Attitudes Toward Participation in Biopsy-Based Kidney Research.

INTRODUCTION: As part of the precision medicine initiative, the National Institutes of Health/National Institute of Diabetes and Digestive Kidney Diseases has proposed collecting human kidney tissue to discover novel therapeutic targets from patients with kidney diseases. Patient attitudes on participating in kidney biopsy-based research are largely unknown. METHODS: We evaluated attitudes toward donating kidney tissue to research among participants who had experienced a clinically indicated kidney biopsy, through a survey conducted 9 months (interquartile range, 5-13 months) after their biopsy. RESULTS: Of the 177 participants contacted, 117 (66%) participated in the survey. A total of 85 participants (73%) reported that they would allow additional needle passes during a clinically indicated biopsy to donate kidney tissue for research. As reasons for participating in such a study, the participants reported the desire to help others and to contribute to science, and the lack of additional burden while participating in such a study. In a multivariable logistic model, older and African American participants had lower odds of allowing an additional pass for research (odds ratio: age ≥65 years [vs. ≤40], 0.15 [95% confidence interval, 0.03-0.73]; African Americans (vs. all others), 0.15 [95% confidence interval, 0.05-0.44]). However, participants' self-reported biopsy complications such as pain, anxiety, and hematuria did not affect their willingness to allow additional passes. A total of 23 participants (20%) stated that they would agree to undergo a biopsy for research even if it was not clinically indicated. CONCLUSION: Among patients who had experienced a kidney biopsy, a majority were amenable to additional needle passes to donate kidney tissue for research during a future, clinically indicated biopsy, whereas a minority would undergo a biopsy for research purpose only.

Blood pressure targets for hemodialysis patients.

The association between blood pressure (BP) and mortality is unique in hemodialysis patients compared with that in the general population. This is because of an altered benefit-risk balance associated with BP reduction in these patients. An adequately designed study comparing BP targets in hemodialysis patients remains to be conducted. The current evidence available to guide dialysis providers regarding treatment strategies for managing hypertension in this population is limited to large observational studies and small randomized controlled trials. In this opinion article, we review these data and discuss the key points regarding BP management for hemodialysis patients. Our aim is to provide a practical opinion regarding BP targets that nephrologists can incorporate into clinical practice, with a focus on moving away from dialysis unit BPs and focusing on out-of-dialysis unit BPs.

Hypertension Management in Transition: From CKD to ESRD.

Hypertension is present in ∼90% of patients in late-stage CKD. There are scarce data focusing on the transition period between CKD Stages 4 and 5 (end-stage kidney disease) as it relates to hypertension evaluation and management. Here, we propose that a combination of the principles used in the management of patients with CKD Stages 4 and 5 be applied to patients in this transition. These include the use of out-of-office blood pressure (BP) monitoring (eg, home BP), avoidance of excessively tight BP goals, emphasis of sodium restriction, preferential use of blockers of the renin-angiotensin system and diuretics, and consideration of the use of beta blockers.

We Hold Antihypertensives Prior To Dialysis.

Hypertension is the most common complication of end-stage renal disease and chronic hemodialysis and yet, only a third of these patients have adequately controlled blood pressures. Pathogenesis of hypertension in this population is complex and multifactorial and therefore poses numerous treatment challenges. Furthermore, it is common practice among nephrologists to withhold antihypertensives prior to a hemodialysis procedure due to concerns for intradialytic hypotension (IDH). Intradialytic hypertension (ID-HTN) is an increasingly recognized phenomenon and although less common than IDH, portends poor cardiovascular prognosis as well as reflects higher hypertension burden in the dialysis population. Withholding antihypertensives prior to dialysis routinely in patients may worsen interdialytic blood pressure control as well as increase the prevalence of euvolemic ID-HTN. It may also increase the risk of cardiac arrhythmias and further compromise hemodynamic stability during dialysis. In such situations, predialysis administration of antihypertensive is appropriate and necessary and drug choice should be based on the patient's comorbidities, pharmacokinetics of the drug and its dialyzability.