hypertension

Diagnosis and Management of Resistant Hypertension: A Review

Author/s: 
Michel Azizi, Wanpen Vongpatanasin, Naomi D. L. Fisher

Importance: Hypertension, defined as office systolic blood pressure (SBP) 130 mm Hg or greater and/or diastolic blood pressure 80 mm Hg or greater, affects 43.9% of women and 49.5% of men in the US. Approximately 19.7% of patients treated for hypertension have apparent resistant hypertension (blood pressure ≥130/80 mm Hg) despite using 3 or more antihypertensive medications, preferably a renin-angiotensin system blocker, a calcium channel blocker, and a thiazide-type diuretic, at maximally tolerated doses.

Observations: Approximately 10% of patients treated for hypertension have true resistant hypertension confirmed with home or 24-hour ambulatory blood pressure monitoring to exclude white-coat hypertension (approximately 37.5% of apparent resistant hypertension) and after excluding medication nonadherence (approximately 50%) and secondary hypertension such as primary aldosteronism (approximately 5%-25%). Conditions associated with resistant hypertension include obesity, diabetes, chronic kidney disease, and sleep apnea. Resistant hypertension is associated with increased risk of cardiovascular death vs controlled blood pressure at 5 years to 10 years (absolute risk increase, 10.3% [95% CI, 8.7%-12.1%]). Lifestyle modifications for resistant hypertension include a low-sodium diet (<1500 mg/d), reducing or avoiding alcohol, 150 min/wk or more of aerobic exercise, and weight loss. Illicit drugs (eg, cocaine) and medications that increase blood pressure (eg, nonsteroid anti-inflammatory drugs, serotonin-norepinephrine reuptake inhibitors) should be avoided. Sleep apnea should be treated when diagnosis is confirmed. Pharmacologic optimization includes use of combination tablets of antihypertensives; intensifying diuretic therapy by using chlorthalidone; and sequential addition of antihypertensive medications using evidence-based algorithms. In a meta-analysis of 20 studies (9 randomized clinical trials [RCTs] and 11 observational studies [331 participants]), use of antihypertensive therapies that combine 2 to 3 medications into a single formulation reduced SBP by -3.99 mm Hg (95% CI, -7.92 to -0.07) vs equivalent doses given separately. For patients with apparent or true resistant hypertension who have an estimated glomerular filtration rate of 45 mL/min/1.73 m2 or greater and a serum potassium level of 4.5 mmol/L or less, adding spironolactone (25-50 mg/d) compared with placebo lowers office SBP by -13.3 mm Hg (95% CI, -17.89 to -8.72 [4 RCTs]) and 24-hour ambulatory SBP by -8.46 mm Hg (95% CI, -12.54 to -4.38 [2 RCTs]) in a network meta-analysis of 24 RCTs (3485 patients with resistant hypertension). A meta-analysis of 10 RCTs (2478 participants) reported that compared with a sham procedure, catheter-based renal denervation, which disrupts the sympathetic nerves in the renal artery walls, decreased 24-hour ambulatory SBP by -4.4 mm Hg (95% CI, -6.1 to -2.7) and office SBP by -6.6 mm Hg (95% CI, -9.7 to -3.6).

Conclusions and relevance: True resistant hypertension affects 10% of patients treated for hypertension and is diagnosed after excluding white-coat hypertension, medication nonadherence, and secondary hypertension such as primary aldosteronism. First-line treatment includes lifestyle modifications, diuretic therapy with chlorthalidone, and combination tablets of antihypertensives. Spironolactone and renal denervation decrease blood pressure in patients with true resistant hypertension.

Management of Orthostatic Hypotension: A Review

Author/s: 
David Moloney, Ayman Youssef, Luis E. Okamoto

Importance: Orthostatic hypotension is a common but underrecognized condition that increases with age and is associated with a lower quality of life, falls, and increased mortality. The frequent coexistence of supine hypertension and postprandial hypotension with orthostatic hypotension makes it a challenging condition to manage.

Observations: Testing for orthostatic hypotension should be done in patients with orthostatic symptoms (eg, vision changes and dizziness that occur only when upright and improve when seated or lying down), as well as asymptomatic patients in high-risk groups such as adults with frailty who are older than 70 years, individuals with neurodegenerative or autonomic disorders, and patients with unexplained falls. Patients with orthostatic hypotension should be screened for postprandial hypotension and supine hypertension to inform the treatment approach. Nonpharmacological strategies, such as medication review, increased salt and fluid intake, compression garments, and behavioral modifications, serve as fundamental approaches to treat orthostatic hypotension. Midodrine and droxidopa are the only US Food and Drug Administration-approved medications for orthostatic hypotension, but other medications (eg, fludrocortisone, atomoxetine, pyridostigmine) are used off label as part of an individualized treatment plan. Treatment targets in orthostatic hypotension are focused not on blood pressure measurements but on symptom relief and fall prevention.

Conclusions and relevance: All patients with orthostatic symptoms-along with other select patient groups-should be evaluated for orthostatic hypotension. Nonpharmacological treatments are first line, and medication decisions should be tailored based on clinical presentation and relevant comorbidities.

Diagnosis and Management of Resistant Hypertension: A Review

Author/s: 
Michel Azizi, Wanpen Vongpatanasin, Naomi D L Fisher, Felix Mahfoud, Laurence Amar, Ajay J Kirtane

Importance: Hypertension, defined as office systolic blood pressure (SBP) 130 mm Hg or greater and/or diastolic blood pressure 80 mm Hg or greater, affects 43.9% of women and 49.5% of men in the US. Approximately 19.7% of patients treated for hypertension have apparent resistant hypertension (blood pressure ≥130/80 mm Hg) despite using 3 or more antihypertensive medications, preferably a renin-angiotensin system blocker, a calcium channel blocker, and a thiazide-type diuretic, at maximally tolerated doses.

Observations: Approximately 10% of patients treated for hypertension have true resistant hypertension confirmed with home or 24-hour ambulatory blood pressure monitoring to exclude white-coat hypertension (approximately 37.5% of apparent resistant hypertension) and after excluding medication nonadherence (approximately 50%) and secondary hypertension such as primary aldosteronism (approximately 5%-25%). Conditions associated with resistant hypertension include obesity, diabetes, chronic kidney disease, and sleep apnea. Resistant hypertension is associated with increased risk of cardiovascular death vs controlled blood pressure at 5 years to 10 years (absolute risk increase, 10.3% [95% CI, 8.7%-12.1%]). Lifestyle modifications for resistant hypertension include a low-sodium diet (<1500 mg/d), reducing or avoiding alcohol, 150 min/wk or more of aerobic exercise, and weight loss. Illicit drugs (eg, cocaine) and medications that increase blood pressure (eg, nonsteroid anti-inflammatory drugs, serotonin-norepinephrine reuptake inhibitors) should be avoided. Sleep apnea should be treated when diagnosis is confirmed. Pharmacologic optimization includes use of combination tablets of antihypertensives; intensifying diuretic therapy by using chlorthalidone; and sequential addition of antihypertensive medications using evidence-based algorithms. In a meta-analysis of 20 studies (9 randomized clinical trials [RCTs] and 11 observational studies [331 participants]), use of antihypertensive therapies that combine 2 to 3 medications into a single formulation reduced SBP by -3.99 mm Hg (95% CI, -7.92 to -0.07) vs equivalent doses given separately. For patients with apparent or true resistant hypertension who have an estimated glomerular filtration rate of 45 mL/min/1.73 m2 or greater and a serum potassium level of 4.5 mmol/L or less, adding spironolactone (25-50 mg/d) compared with placebo lowers office SBP by -13.3 mm Hg (95% CI, -17.89 to -8.72 [4 RCTs]) and 24-hour ambulatory SBP by -8.46 mm Hg (95% CI, -12.54 to -4.38 [2 RCTs]) in a network meta-analysis of 24 RCTs (3485 patients with resistant hypertension). A meta-analysis of 10 RCTs (2478 participants) reported that compared with a sham procedure, catheter-based renal denervation, which disrupts the sympathetic nerves in the renal artery walls, decreased 24-hour ambulatory SBP by -4.4 mm Hg (95% CI, -6.1 to -2.7) and office SBP by -6.6 mm Hg (95% CI, -9.7 to -3.6).

Conclusions and relevance: True resistant hypertension affects 10% of patients treated for hypertension and is diagnosed after excluding white-coat hypertension, medication nonadherence, and secondary hypertension such as primary aldosteronism. First-line treatment includes lifestyle modifications, diuretic therapy with chlorthalidone, and combination tablets of antihypertensives. Spironolactone and renal denervation decrease blood pressure in patients with true resistant hypertension.

Management of Hypertension in Adults

Author/s: 
Amber E Johnson, Christopher D Jackson, Jason T Alexander

Hypertension is the leading modifiable risk factor worldwide for ASCVD, and approximately half of US adults have hypertension.1 Uncontrolled BP contributes to heart failure, stroke, atrial fibrillation, and sudden cardiac death and is associated with development of kidney failure and dementia.2 This guideline was designed to provide clinicians with a risk stratification approach to managing BP. This synopsis highlights key guideline recommendations.

Hypertension and alcohol: a cross-sectional study comparing PEth with AUDIT and AUDIT-C in primary care

Author/s: 
Åsa Thurfjell, Maria Hagströmer, Charlotte Ivarsson, Anders Norrman, Johanna Adami, Lena Lundh, Jan Hasselström

Background: This cross-sectional study aimed to describe proportions of patients with indications of alcohol consumption using phosphatidylethanol (PEth), the Alcohol Use Disorders Identification Test (AUDIT), and its consumption-focused version (AUDIT-C), in relation to blood pressure (BP) control, overall and by sex.

Methods: A total of 270 hypertensive primary care patients (ICD-10: I10.9) were stratified into BP control groups: controlled (<140/90 mmHg), uncontrolled (≥140/90 mmHg), and apparent treatment-resistant hypertension (aTRH; ≥140/90 mmHg with ≥3 antihypertensive drugs). A randomized sample from each stratum was invited, baseline data were collected. Alcohol consumption using predefined categories for PEth and AUDIT, and hazardous use (PEth ≥ 0.122 µmol/L; AUDIT ≥ 8; AUDIT-C ≥ 5 for men, ≥4 for women), were analyzed in relation to BP control groups.

Results: Mean age was 67 ± 11 years; 42% were women. PEth indicated high and regular alcohol consumption in 6.4% of controlled, 5.3% of uncontrolled, and 19.2% of aTRH patients (controlled vs. aTRH, P = .027; uncontrolled vs. aTRH, P = .013). AUDIT showed no significant differences in hazardous use between BP groups (P = .865). AUDIT-C identified slightly higher proportions of hazardous use than PEth, across BP groups and sexes. No significant differences were found between BP groups for hazardous use by PEth (P = .339) or AUDIT-C (P = .150).

Conclusions: PEth revealed significantly higher alcohol use in the aTRH group, undetected by AUDIT. AUDIT-C and PEth identified more hazardous use than AUDIT, suggesting their potential to prompt alcohol-related discussions and support evidence-based hypertension care. PEth correlated more strongly with AUDIT-C than with AUDIT.

Clinical trial registration: Retrospectively registered in Clinical Trials, SLSO2022-0143, 2022-12-10.

Keywords: alcohol use disorder; cardiovascular disorders (hypertension/DVT/atherosclerosis); hypertension (high blood pressure); prevention; primary care; screening.

Approach to pelvic venous disorders

Author/s: 
Andrew D Brown

Objective: To provide a practical guide to help family physicians recognize, diagnose, and manage patients with pelvic venous disorders (PeVDs), often overlooked as causes of chronic pelvic pain and varicose veins.

Sources of information: This review is based on guidelines from the American Venous Forum, the Society for Vascular Surgery, the American Vein and Lymphatic Society, the Society of Interventional Radiology, and the European Society for Vascular Surgery.

Main message: PeVDs are common, though frequently misdiagnosed, causes of chronic pelvic pain and varicose veins predominantly in female patients. These conditions arise from venous reflux or obstruction, which can cause varicose veins and venous hypertension in the renal hilum, pelvis, perineum, and lower extremities. Family physicians should recognize the clinical signs of PeVDs and use appropriate imaging to confirm diagnoses. Interventional treatments, including embolization and stenting, are effective for symptom management and improving patient outcomes.

Conclusion: Early recognition of patients with PeVDs by family physicians is crucial for timely and effective treatment. By using appropriate diagnostic tools and making timely referrals, physicians can substantially improve patients' quality of life.

Chlorthalidone vs. Hydrochlorothiazide for Hypertension–Cardiovascular Events

Author/s: 
Ishani, A., Cushman, W. C., Leatherman, S. M., R. A., Woods, P., Glassman, P. A., Taylor, A. A., Hau, C., Klint, A., Huang, G. D., Brophy, M. T., Fiore, L. D., Ferguson, R. E., Diuretic Comparison Project Writing Group

Background: Whether chlorthalidone is superior to hydrochlorothiazide for preventing major adverse cardiovascular events in patients with hypertension is unclear.

Methods: In a pragmatic trial, we randomly assigned adults 65 years of age or older who were patients in the Department of Veterans Affairs health system and had been receiving hydrochlorothiazide at a daily dose of 25 or 50 mg to continue therapy with hydrochlorothiazide or to switch to chlorthalidone at a daily dose of 12.5 or 25 mg. The primary outcome was a composite of nonfatal myocardial infarction, stroke, heart failure resulting in hospitalization, urgent coronary revascularization for unstable angina, and non-cancer-related death. Safety was also assessed.

Results: A total of 13,523 patients underwent randomization. The mean age was 72 years. At baseline, hydrochlorothiazide at a dose of 25 mg per day had been prescribed in 12,781 patients (94.5%). The mean baseline systolic blood pressure in each group was 139 mm Hg. At a median follow-up of 2.4 years, there was little difference in the occurrence of primary-outcome events between the chlorthalidone group (702 patients [10.4%]) and the hydrochlorothiazide group (675 patients [10.0%]) (hazard ratio, 1.04; 95% confidence interval, 0.94 to 1.16; P = 0.45). There were no between-group differences in the occurrence of any of the components of the primary outcome. The incidence of hypokalemia was higher in the chlorthalidone group than in the hydrochlorothiazide group (6.0% vs. 4.4%, P<0.001).

Conclusions: In this large pragmatic trial of thiazide diuretics at doses commonly used in clinical practice, patients who received chlorthalidone did not have a lower occurrence of major cardiovascular outcome events or non-cancer-related deaths than patients who received hydrochlorothiazide. (Funded by the Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT02185417.).

Effects of salt substitutes on clinical outcomes: a systematic review and meta-analysis

Author/s: 
Yin, X., Rodgers, A., Perkovic, A., Huang, L., Li, K., Yu, J., Wu, Y., Wu, J. H. Y., Marklund, M., Huffman, M. D., Miranda, J. J., Di Tanna, G. L., Labarthe, D., Elliott, P., Tian, M., Neal, B.

Objectives The Salt Substitute and Stroke Study (SSaSS) recently reported blood pressure-mediated benefits of a potassium-enriched salt substitute on cardiovascular outcomes and death. This study assessed the effects of salt substitutes on a breadth of outcomes to quantify the consistency of the findings and understand the likely generalisability of the SSaSS results.

Methods We searched PubMed, Embase and the Cochrane Library up to 31 August 2021. Parallel group, step-wedge or cluster randomised controlled trials reporting the effect of salt substitute on blood pressure or clinical outcomes were included. Meta-analyses and metaregressions were used to define the consistency of findings across trials, geographies and patient groups.

Results There were 21 trials and 31 949 participants included, with 19 reporting effects on blood pressure and 5 reporting effects on clinical outcomes. Overall reduction of systolic blood pressure (SBP) was −4.61 mm Hg (95% CI −6.07 to −3.14) and of diastolic blood pressure (DBP) was −1.61 mm Hg (95% CI −2.42 to −0.79). Reductions in blood pressure appeared to be consistent across geographical regions and population subgroups defined by age, sex, history of hypertension, body mass index, baseline blood pressure, baseline 24-hour urinary sodium and baseline 24-hour urinary potassium (all p homogeneity >0.05). Metaregression showed that each 10% lower proportion of sodium choloride in the salt substitute was associated with a −1.53 mm Hg (95% CI −3.02 to −0.03, p=0.045) greater reduction in SBP and a −0.95 mm Hg (95% CI −1.78 to −0.12, p=0.025) greater reduction in DBP. There were clear protective effects of salt substitute on total mortality (risk ratio (RR) 0.89, 95% CI 0.85 to 0.94), cardiovascular mortality (RR 0.87, 95% CI 0. 81 to 0.94) and cardiovascular events (RR 0.89, 95% CI 0.85 to 0.94).

Conclusions The beneficial effects of salt substitutes on blood pressure across geographies and populations were consistent. Blood pressure-mediated protective effects on clinical outcomes are likely to be generalisable across population subgroups and to countries worldwide.

Screening for Hypertension in Adults

Author/s: 
U.S. Preventative Services Task Force

IMPORTANCE Hypertension is a prevalent condition that affects approximately 45% of the adult US population and is the most commonly diagnosed condition at outpatient office visits. Hypertension is a major contributing risk factor for heart failure, myocardial infarction, stroke, and chronic kidney disease. OBJECTIVE To reaffirm its 2015 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for hypertension in adults, the accuracy of office blood pressure measurement for initial screening, and the accuracy of various confirmatory blood pressure measurement methods. POPULATION Adults 18 years or older without known hypertension. EVIDENCE ASSESSMENT Using a reaffirmation deliberation process, the USPSTF concludes with high certainty that screening for hypertension in adults has substantial net benefit. RECOMMENDATION The USPSTF recommends screening for hypertension in adults 18 years or older with office blood pressure measurement. The USPSTF recommends obtaining blood pressure measurements outside of the clinical setting for diagnostic confirmation before starting treatment. (A recommendation)

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