Benefits outweigh harms/burden Benefits slightly outweigh harms/ burden Benefits and harms/burden are balanced Harms/burden slightly outweigh benefits Harms/burden outweigh benefits Confidence in the quality of the evidence Is there high or moderate quality evidence that answers this question? What is the overall certainty of this evidence? High Moderate Low Very low Values and preferences Are you confident about the typical values and preferences and are they similar across the target population? What are the patient s values and preferences? Are the assumed or identified relative values similar across the target population? Similar values Some variation Large variation Other implications (e.g., resource use, equity, acceptability, feasibility, subgroup considerations) Are the resources worth the expected net benefit from the recommendation? What are the costs per resource unit? Is this intervention generally available? Is this intervention and its effects worth withdrawing or not allocating resources from other interventions? Is there lots of variability in resource requirements across settings? Various considerations The strength of a recommendation is defined as the extent to which one can be confident that the desirable effects of an intervention outweigh its undesirable effects and is based on the framework above, which combines the four domains.[158] GRADE methodology does not allow for recommendations to be made based on expert opinion alone. While strong recommendations are usually based on high or moderate confidence in the estimates of effect (quality of the evidence) there may be instances where strong recommendations are warranted even when the quality of evidence is low.[18] In these types of instances where the balance of desirable and undesirable outcomes and values and preferences played large roles in determining the strength of a recommendation, this is explained in the discussion section for the recommendation. The GRADE of a recommendation is based on the following elements: Four decision domains used to determine the strength and direction (described above) Relative strength (Strong or Weak) Direction (For or Against) The relative strength of the recommendation is based on a binary scale, Strong or Weak. A strong recommendation indicates that the Work Group is highly confident that desirable outcomes outweigh undesirable outcomes. If the Work Group is less confident of the balance between desirable and undesirable outcomes, they present a weak recommendation. Similarly, a recommendation for a therapy or preventive measure indicates that the desirable consequences outweigh the undesirable consequences. A recommendation against a therapy or preventive measure indicates that the undesirable consequences outweigh the desirable consequences. Occasionally, instances may occur when the Work Group feels there is insufficient evidence to make a recommendation for or against a specific therapy or preventive measure. This can occur when there is an absence of studies on a particular topic that met evidence review inclusion criteria, studies included in the evidence review report conflicting results, or studies included in the evidence review report inconclusive results regarding the desirable and undesirable outcomes. Using these elements, the grade of each recommendation is presented as part of a continuum: Strong For (or We recommend offering this option ) Weak For (or We suggest offering this option ) No recommendation for or against (or There is insufficient evidence ) Weak Against (or We suggest not offering this option ) Strong Against (or We recommend against offering this option ) Note that weak (For or Against) recommendations may also be termed Conditional, Discretionary, or Qualified. Recommendations may be conditional based upon patient values and preferences, the resources available, or the setting in which the intervention will be implemented. Recommendations may be at the discretion of the patient and clinician or they may be qualified with an explanation about the issues that would lead decisions to vary. E. Recommendation Categorization a. Recommendation Categories and Definitions A set of recommendation categories was adapted from those used by NICE.[21,22] These categories, along with their corresponding definitions, were used to account for the various ways in which recommendations could have been updated from the 2014 VA/DoD HTN CPG. The categories and definitions can be found in Table A-5. Table A-5. Recommendation Categories and Definitions* Evidence Reviewed* Recommendation Category Definition Reviewed New-added New recommendation following review of the evidence New-replaced Recommendation from previous CPG that has been carried over to the updated CPG that has been changed following review of the evidence Not changed Recommendation from previous CPG that has been carried forward to the updated CPG where the evidence has been reviewed but the recommendation is not changed Amended Recommendation from the previous CPG that has been carried forward to the updated CPG where the evidence has been reviewed and a minor amendment has been made Deleted Recommendation from the previous CPG that has been removed based on review of the evidence Not reviewed Not changed Recommendation from previous CPG that has been carried forward to the updated CPG, but for which the evidence has not been reviewed Amended Recommendation from the previous CPG that has been carried forward to the updated CPG where the evidence has not been reviewed and a minor amendment has been made Deleted Recommendation from the previous CPG that has been removed because it was deemed out of scope for the updated CPG *Adapted from the NICE guideline manual (2012) [21] and Garcia et al. (2014) [22] Abbreviation: CPG: clinical practice guideline b. Categorizing Recommendations with an Updated Review of the Evidence Recommendations were first categorized by whether or not they were based on an updated review of the evidence. If evidence had been reviewed, recommendations were categorized as New-added, New- replaced, Not changed, Amended, or Deleted. Reviewed, New-added recommendations were original, new recommendations that were not in the 2014 VA/DoD HTN CPG. Reviewed, New-replaced recommendations were in the previous version of the guideline, but were modified to align with the updated review of the evidence. These recommendations could have also included clinically significant changes to the previous version. Recommendations categorized as Reviewed, Not changed were carried forward from the previous version of the CPG unchanged. The Reviewed, Not Changed category was used for recommendations carried forward to the updated CPG with review of the evidence and where no changes were deemed necessary to the recommendation language. For recommendations carried forward to the updated CPG with review of the evidence and slightly modified wording, the Reviewed, Amended recommendation category was used. This allowed for the wording of the recommendation to reflect GRADE methodology as well as for any other non- substantive (i.e., not clinically meaningful) language changes deemed necessary. The evidence used to support these recommendations was carried forward from the previous version of the CPG and/or was identified in the evidence review for the update. Recommendations could have also been designated Reviewed, Deleted. These were recommendations from the previous version of the CPG that were not brought forward to the updated guideline after review of the evidence. This occurred if the evidence supporting the recommendations was out of date, to the extent that there was no longer any basis to recommend a particular course of care and/or new evidence suggests a shift in care, rendering recommendations in the previous version of the guideline obsolete. c. Categorizing Recommendations without an Updated Review of the Evidence There were also cases in which it was necessary to carry forward recommendations from the previous version of the CPG without an updated SR of the evidence. Due to time and budget constraints, the update of the HTN CPG could not include a review of all available evidence on management of HTN; instead, the KQs were focused on areas of new or updated scientific research or areas that were not previously covered in the CPG. For areas of research that have not changed, and for which recommendations made in the previous version of the guideline were still relevant, recommendations could have been carried forward to the updated guideline without an updated SR of the evidence. The support for these recommendations in the updated CPG was thus also carried forward from the previous version of the CPG. These recommendations were categorized as Not reviewed. If evidence had not been reviewed, recommendations could have been categorized as Not changed, Amended, or Deleted. Not reviewed, Not changed recommendations refer to recommendations from the previous version of the HTN CPG that were carried forward unchanged to the updated version. The category of Not reviewed, Amended was used to designate recommendations that were modified from the 2014 VA/DoD HTN CPG with the updated GRADE language, as explained above. Recommendations could also have been categorized as Not reviewed, Deleted if they were determined to be out of scope. A recommendation was out of scope if it pertained to a topic (e.g., population, care setting, treatment, and condition) outside of the scope for the updated CPG as defined by the Work Group. The categories for the recommendations included in the 2020 version of the guideline are noted in the Recommendations. The categories for the recommendations from the 2014 VA/DoD HTN CPG are noted in Appendix D. F. Drafting and Submitting the Final Clinical Practice Guideline Following the face-to-face meeting, the Champions and Work Group members were given writing assignments to craft discussion sections to support each of the new recommendations and/or to update discussion sections from the 2014 VA/DoD HTN CPG to support the amended carried forward recommendations. The Work Group also considered tables, appendices, and other sections from the 2014 VA/DoD HTN CPG for inclusion in the update. During this time, the Champions and Work Group also made additional revisions to the algorithms, as necessary. After developing the initial draft of the updated CPG, an iterative review process was used to solicit feedback on and make revisions to the CPG. Once they were developed, the first two drafts of the CPG were posted on a wiki website for a period of 14-20 business days for internal review and comment by the Work Group. All feedback submitted during each review period was reviewed and discussed by the Work Group and appropriate revisions were made to the CPG. Draft 3 of the CPG was made available for peer review and comment. This process is described in the section titled Peer Review Process. After revisions were made based on the feedback received during the peer review and comment period, the Champions presented the CPG to the EBPWG for their approval. Changes were made based on feedback from the EBPWG and the guideline was finalized. The Work Group also produced a set of guideline toolkit materials which included a provider summary, pocket card, and patient summary. The final 2020 VA/DoD HTN CPG was submitted to the EBPWG in March 2020. Appendix B: Patient Focus Group Methods and Findings A. Methods As part of the effort to update this CPG, VA and DoD Leadership held a patient focus group. The patient focus group was held on January 23, 2019, at the Naval Medical Center in San Diego, CA. The aim of the focus group was to further understand and incorporate the perspective of patients with HTN and who are covered and/or receiving their care through the VA and/or DoD healthcare systems, as these patients are most affected by the recommendations put forth in the CPG. The focus group delved into the patients perspectives on a set of topics related to their HTN management, including their priorities, challenges they have experienced, the information they received regarding their care, as well as the impacts of their care on their lives. Participants for the focus group were recruited by VA and DoD Leadership as well as by the HTN CPG Champions. Patient focus group participants were not intended to be a representative sample of VA and DoD patients. However, recruitment focused on eliciting a range of perspectives likely to be relevant and informative in the guideline development process. Patients were not incentivized for their participation or reimbursed for travel expenses. The HTN CPG Champions and Work Group, with support from Lewin, developed a set of questions to help guide the focus group. The focus group facilitator led the discussion using the previously prepared questions as a general guide to elicit the most important information from the patients regarding their experiences and views about their treatment and overall care. Given the limited time and the range of interests of the focus group participants, not all of the listed questions were addressed. B. Findings a. Provide comprehensive information and education to patients regarding their condition, management strategies, and self-management, including expanding available information on complementary and alternative therapies. Patients would like to be offered educational materials (e.g., pamphlets) as well as verbal communication of pertinent information related to their condition. Some of the patients felt that their providers did not offer the full range of management options available and seemed to prioritize pharmacologic interventions. Patients noted that there were many non-pharmacological management strategies that had not been offered to them and/or they were not aware of, including Tai Chi, yoga, meditation, etc. Some of the patients felt that their providers did not consider all of their individual, unique characteristics that could impact their high blood pressure and management strategies. Several patients mentioned that they did not receive information on the harms of having high blood pressure, including the increased risk of stroke, heart disease, etc. (i.e., education on the importance of treating and managing high blood pressure). Patients would like communication around the AEs of medication. Patients raised concern over AEs of medication and some noted that they wanted to avoid use of medications, when possible. b. Improve the method of measuring blood pressure in the office. Patients noted that when their blood pressure was measured by machine in the office setting, they experienced pain and uncomfortable pressure. Some of the patients noted that their blood pressure had to be taken twice when in the office setting, the first reading rarely being accurate. Patients felt that the office blood pressure readings were inaccurate; they trusted the devices they use at home more. There were noticeable differences between blood pressure readings when it was taken manually versus a machine. c. Education around home monitoring devices and strategies for measurement and management, including frequency of measurement, is important. All patients noted that they have a device to monitor their blood pressure at home, however, none of the patients had received instruction from their provider about how to use the device to measure their own blood pressure. None of the patients reported having learned from their provider how often to measure their blood pressure at home; the patients all reported different frequencies of self-monitoring their blood pressure. d. Improve communication between providers and patients, considering patient preferences regarding frequency of communication and mode of communication. Patients felt that providers should listen actively to their patients and take into consideration the patient s other medical conditions (e.g., co-occurring diabetes, injuries/physical limitations) and needs that may affect their treatment to provide a holistic approach to managing their HTN. Some patients appreciated and/or felt they would benefit from additional contact with their providers in between their annual or bi-annual visits. All patients were interested in telehealth modalities to improve communication with their providers and were willing to engage with providers through phone calls, email, or mobile applications. e. All patients understood the importance of lifestyle modifications to lower their blood pressure. All of the patients reported closely monitoring and changing their diet when they learned of their HTN diagnosis. All of the patients understood that they should decrease sodium and alcohol intake and should not smoke. Most of the patients noted that they put a strong emphasis on staying active to improve their blood pressure. Patients were interested in other complementary alternative therapies to improve their blood pressure, such as meditation, yoga, and acupuncture. Appendix C: Evidence Table Table C-1. Evidence Tablea,b,c Recommendation 2014 Strength of Recommendation Evidence 2020 Strength of Recommendation Recommendation Category 1. We recommend screening adults for elevated blood pressure periodically. Strong for Additional References: Strong for Not Reviewed, Amended 2. We suggest using attended or unattended, fully automated office blood pressure measurement (programmed to wait five minutes and record the average of three measurements separated by at least 30 seconds). N/A Additional References: Weak for Reviewed, New- added 3. When fully automated blood pressure measurement is not available, we suggest measurement of blood pressure using standard technique and a properly calibrated and validated sphygmomanometer. Strong for Additional References: Weak for Reviewed, New- replaced 4. We suggest using out-of-office blood pressure monitoring methods (ambulatory 24-hour monitoring or home blood pressure measurements) to inform the diagnosis and management of hypertension. Strong for, Weak for Additional References: Weak for Reviewed, New- replaced 5. Among patients treated for hypertension, we suggest offering home blood pressure self-monitoring with co- interventions for lowering systolic and diastolic blood pressure. N/A [49-53] Weak for Reviewed, New- added a Strength of Recommendation columns: Refer to the Grading Recommendations section for more information on how the strength of the recommendation was determined using GRADE methodology. b Evidence column: The first set of references listed in each row in the evidence column constitutes the evidence base for the recommendation. To be included in the evidence base for a recommendation, a reference needed to be identified through the evidence review carried out as part of this guideline update or included in the evidence base for the 2014 VA/DoD HTN CPG. The second set of references in the evidence column (called Additional References ) includes references that provide additional information related to the recommendation, but which were not systematically identified through a literature review. These references were not included in the evidence base for the recommendation and therefore did not influence the strength and direction of the recommendation. c Recommendation Categorization column: Refer to the Recommendation Categorization section for more information on the description of the categorization process and the definition of each category. Recommendation 2014 Strength of Recommendation Evidence 2020 Strength of Recommendation Recommendation Category 6. For all patients, including those with type 2 diabetes, we suggest treating to a systolic blood pressure goal of <130 mm Hg. N/A Additional References: Weak for Reviewed, New- added 7. For patients 60 years and over, we recommend treating to a systolic blood pressure goal of <150 mm Hg with added benefit to lowering systolic blood pressure further for those between 130 mm Hg and 150 mm Hg. Strong For, Strong for Additional References: Strong for Reviewed, Amended 8. For patients 60 years and over with type 2 diabetes, we recommend treating to a systolic blood pressure goal of <140 mm Hg with added benefit to lowering systolic blood pressure further for those between 130 mm Hg and 140 mm Hg. Weak for [54,59,64-68] Strong for Reviewed, Amended 9. For patients 30 years and over, we recommend treating to a diastolic blood pressure goal of <90 mm Hg. Strong for Additional References: Weak for Reviewed, Amended 10. We recommend offering pharmacist-led medication management as an option for patients with hypertension. Weak for [75-81] Strong for Reviewed, New- replaced 11. We suggest offering nurse-led interventions as an option for patients treated for hypertension. Weak for [82-88] Weak for Reviewed, New- replaced 12. We suggest offering registered dietitian-led nutrition interventions as an option for patients with hypertension who are or are not on medication. Weak for Weak for Reviewed, New- replaced 13. We suggest technology-based interventions (e.g., e-counseling, electronic transmission of data, telemonitoring, mobile applications) for improving control of hypertension. Weak for Additional References: Weak for Reviewed, New- replaced 14. We suggest advising patients with hypertension and overweight/obesity to lose weight to improve blood pressure. Strong for [102-109] Weak for Reviewed, Amended 15. For patients with hypertension and overweight/obesity, we suggest offering a diet directed at weight loss for the treatment of hypertension. N/A [106-108] Weak for Reviewed, New- added Recommendation 2014 Strength of Recommendation Evidence 2020 Strength of Recommendation Recommendation Category 16. For the treatment of hypertension, there is insufficient evidence for or against offering weight loss medications for patients with obesity and hypertension. Neither for nor against Reviewed, New- added 17. For the treatment of hypertension, there is insufficient evidence to suggest for or against bariatric surgery for patients with obesity and hypertension. Neither for nor against Reviewed, New- added 18. We suggest offering individual or group-based exercise for the treatment of hypertension to reduce blood pressure. Strong for [111-119] Weak for Reviewed, Amended 19. We recommend a target for aerobic exercise of at least 120 minutes per week for reduction in blood pressure. Strong for [120,121] Strong for Not Reviewed, Amended 20. We recommend a dietitian-led Dietary Approaches to Stop Hypertension Diet for the treatment or prevention of hypertension for patients with hypertension or interested patients with other cardiovascular risk factors. Strong for [122-124] Strong for Not Reviewed, Amended 21. In patients with hypertension, we recommend that sodium intake be limited to no more than 2,300 mg/day (100 mmol/day), with referral to a dietitian or other support as appropriate. Strong for Additional References: Strong for Not Reviewed, Not Changed 22. In patients with additional cardiovascular risk factors, such as dyslipidemia, we suggest considering a dietitian- led Mediterranean Diet as an alternative to the Dietary Approaches to Stop Hypertension Diet. Weak for Additional References: Weak for Not Reviewed, Not Changed 23. We recommend offering a thiazide-type diuretic, calcium channel blocker, or either an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker as primary pharmacologic therapy for hypertension for reduction in composite cardiovascular outcomes. Strong for, Strong for [135] Strong for Reviewed, New- replaced 24. In African American patients with hypertension, we recommend against using an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker as monotherapy. Strong against [136-141] Strong against Reviewed, Not Changed 25. In hypertensive patients 65 years and over, we suggest a thiazide-type diuretic for reduction in composite cardiovascular outcomes. N/A [137,142-144] Weak for Reviewed, New- added Recommendation 2014 Strength of Recommendation Evidence 2020 Strength of Recommendation Recommendation Category 26. We recommend against more than one of the following three drug classes together in the same patient: angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or direct renin inhibitors. Strong against Additional References: Strong against Not Reviewed, Not Changed 27. For the treatment of hypertension, there is insufficient evidence to recommend for or against initiating combination therapy over initiating monotherapy with the sequential addition of another medication. Weak for Additional References: Neither for nor against Reviewed, New- replaced 28. For patients with resistant hypertension (defined as those who are not adequately controlled with maximally tolerated dose of triple therapy [i.e., a thiazide-type diuretic, calcium channel blockers, and angiotensin- converting enzyme inhibitor or angiotensin II receptor blocker]), we suggest adding spironolactone in those patients without contraindications. Strong for Additional References: Weak for Reviewed, New- replaced Appendix D: 2014 Recommendation Categorization Table Table D-1. 2014 Recommendation Categorization Tablea,b,c,d,e 2014 Recommendation Text 2014 Strength of Recommendation Recommendation Category Recommendation Section Number Page We recommend screening adults for elevated blood pressure occur periodically, preferably annually. (Modified from 2004 VA/DoD HTN CPG without an updated systematic review of the evidence.*) Strong for Not reviewed, Amended We suggest that screening occur at the time of routine preventive care or routine health assessment. (Modified from 2004 VA/DoD HTN CPG without an updated systematic review of the evidence.) Weak for Not reviewed, Deleted We recommend the diagnosis of hypertension be determined based on at least two blood pressure readings on two separate patient visits. (Modified from 2004 VA/DoD HTN CPG without an updated systematic review of the evidence.) Strong for Not reviewed, Deleted We recommend that blood pressure be measured with a technique recommended for the measurement of blood pressure in adults using a properly calibrated and validated sphygmomanometer. (Modified from 2004 VA/DoD HTN CPG without an updated systematic review of the evidence.) Strong for Reviewed, New- replaced For patients whose diagnosis of hypertension remains uncertain, we recommend offering home blood pressure monitoring to confirm diagnosis prior to beginning pharmacologic treatment. (Two to three times a day for seven consecutive days, disregard the first day and take the average of measurements.) Strong for Reviewed, New- replaced a 2014 Location columns: The first three columns indicate the location of each recommendation within the 2014 VA/DoD HTN CPG. b 2014 Recommendation Text column: The 2014 Recommendation Text column contains the wording of each recommendation from the 2014 VA/DoD HTN CPG. c 2014 Strength of Recommendation column: Refer to the Grading Recommendations section for more information on how the strength of the recommendation was determined using GRADE methodology. d Recommendation Category column: The Recommendation Category column indicates the way in which each 2014 VA/DoD HTN CPG recommendation was updated. e 2020 Recommendation column: For recommendations that were carried forward to the 2020 VA/DoD HTN CPG, this column indicates the new recommendation(s) to which they correspond. 2014 Recommendation Text 2014 Strength of Recommendation Recommendation Category Recommendation Section Number Page For patients whose diagnosis of hypertension remains uncertain, we suggest offering 24-hour ambulatory blood pressure monitoring as an alternative to home blood pressure monitoring to confirm diagnosis prior to beginning pharmacologic treatment. Weak for Reviewed, New- replaced We suggest offering a multi-modal approach to adherence interventions, which could include telemonitoring, multi-disciplinary group medical appointments, (e.g., shared medical appointments), case management (by pharmacists, nurses, social workers), patient and provider education, behavioral therapy, etc. Weak for Reviewed, New- replaced We recommend offering lifestyle modification interventions for patients with prehypertension or hypertension based on patient indications and preferences as well as assessment of available local resources. (Modified from 2004 VA/DoD HTN CPG) Strong for Reviewed, Amended We recommend discussing healthy weight range and advising overweight or obese hypertensive patients to reduce their body mass index to below 25. (Modified from 2004 VA/DoD HTN CPG) Strong for Reviewed, Deleted If a normal body mass index (<25) cannot be achieved, we suggest advising patient that a weight reduction of at least 10 pounds can achieve a decrease in blood pressure. Weak for Not reviewed, Deleted We recommend a target for aerobic exercise of 30 to 45 minutes per session, at least four times per week. (Modified from 2004 VA/DoD HTN CPG) Strong for Not reviewed, Amended We suggest the use of a self-monitoring device (e.g., pedometer, mobile apps, etc.) to increase adherence to physical activity. Weak for Reviewed, Deleted For patients interested in complementary and alternative medicine, we suggest considering mind-body therapies such as transcendental meditation or yoga. Weak for Reviewed, Deleted We suggest not offering Tai Chi for the treatment of hypertension as there is a moderate body of evidence that shows this intervention does not reduce blood pressure. Weak against Reviewed, Deleted 2014 Recommendation Text 2014 Strength of Recommendation Recommendation Category Recommendation Section Number Page We recommend a dietitian-led Dietary Approaches to Stop Hypertension (DASH) Diet for the treatment and/or prevention of hypertension for patients with hypertension and/or interested patients with prehypertension and other cardiovascular risk factors. (Modified from 2004 VA/DoD HTN CPG) Strong for Not reviewed, Amended In patients with additional cardiovascular risk factors, such as dyslipidemia, we suggest considering a dietitian-led Mediterranean Diet as an alternative to the DASH Diet. Weak for Not reviewed, Not changed We recommend against the use of soy protein supplements for the treatment of hypertension. Strong against Not reviewed, Deleted In patients with hypertension or prehypertension, we recommend that sodium intake be limited to no more than 2300mg/day (100 mmol/day), with referral to a dietitian or other support as appropriate. (Modified from 2004 VA/DoD HTN CPG) Strong for Not reviewed, Not changed We recommend advising hypertensive and prehypertensive patients to limit alcohol intake to no more than 1 oz per day for men or 0.5 oz of alcohol per day for women. (This is approximately 2 drinks/day in men and 1 drink/day in women, where a drink is 1.5 oz 80-proof liquor, 12 oz beer, or 5 oz wine [all 14g]). (Modified from 2004 VA/DoD HTN CPG) Strong for Not reviewed, Deleted We recommend offering pharmacologic treatment for hypertensive patients 60 years and older with a systolic blood pressure 160 mmHg. Strong for Not reviewed, Deleted We suggest considering pharmacologic treatment using a shared decision-making model for hypertensive patients 60 years and older with systolic blood pressure <160 mmHg. Weak for Not reviewed, Deleted We suggest offering pharmacologic treatment to patients with a history of cerebrovascular disease (stroke, transient ischemic attack, or asymptomatic carotid artery disease) and a systolic blood pressure 140 mmHg. Weak for Not reviewed, Deleted We suggest pharmacologic treatment for hypertensive patients younger than 60 with a systolic blood pressure 160 mmHg, regardless of diastolic blood pressure. Weak for Not reviewed, Deleted 2014 Recommendation Text 2014 Strength of Recommendation Recommendation Category Recommendation Section Number Page We recommend offering pharmacologic treatment for patients 30 years and older with a diastolic blood pressure 90 mmHg. Strong for Not reviewed, Deleted We suggest offering pharmacologic treatment for patients age 18 to 29 with a diastolic blood pressure 90 mmHg. Weak for Not reviewed, Deleted For patients 60 years and over, we recommend treating to a systolic blood pressure goal of <150 mmHg. Strong for Reviewed, Amended Recommendation 7 For patients below 60 years of age, we suggest treating to a systolic blood pressure goal of <150 mmHg. Weak for Reviewed, Deleted We recommend treating to a diastolic blood pressure goal <90 mmHg in patients 30 years and older. Strong for Reviewed, Amended Recommendation 9 We suggest treating to a diastolic blood pressure goal <90 mmHg in patients age 18 to 29. Weak for Reviewed, Deleted For patients with diabetes (all age groups), we recommend treating to a systolic blood pressure goal of <150 mmHg. Strong for Reviewed, Amended Recommendation 7 For patients with diabetes (all age groups) who tolerate antihypertensive drugs, we suggest treating to a systolic blood pressure goal of <140 mmHg. Weak for Reviewed, Amended Recommendation 8 For patients with diabetes, we recommend treating to a diastolic blood pressure goal <85 mmHg. Strong for Reviewed, Deleted We suggest that patients be seen within one month of initiation of lifestyle or pharmacological therapy to determine adequacy of hypertension control, degree of patient adherence, and presence of adverse effects. (Modified from 2004 VA/DoD HTN CPG without an updated systematic review of the evidence.) Weak for Reviewed, Deleted Once the patient s blood pressure is controlled, we suggest follow-up at least annually, or more frequently as indicated, depending on patient preference. (Modified from 2004 VA/DoD HTN CPG without an updated systematic review of the evidence.) Weak for Reviewed, Deleted We suggest taking into consideration the patient s baseline blood pressure and presence of comorbidities, when deciding on either monotherapy or combination therapy (two drugs) when initiating drug therapy. (Modified from 2004 VA/DoD HTN CPG without an updated systematic review of the evidence.) Weak for Reviewed, New- replaced 2014 Recommendation Text 2014 Strength of Recommendation Recommendation Category Recommendation Section Number Page We suggest initiating combination therapy for patients with a baseline systolic blood pressure of >20 mmHg or diastolic blood pressure of >10 mmHg above the patient s goal. (Modified from 2004 VA/DoD HTN CPG without an updated systematic review of the evidence.) Weak for Not reviewed, Deleted We recommend the use of thiazide-type diuretics for the treatment of hypertension. Strong for Reviewed, New- replaced We suggest the use of thiazide-type diuretics at recommended treatment doses as first-line therapy for drug treatment of hypertension either as monotherapy or in combination with other agents. (Modified from 2004 VA/DoD HTN CPG) Weak for Reviewed, Deleted To initiate treatment of hypertension with a thiazide-type diuretic, we suggest the use of chlorthalidone or indapamide over hydrochlorothiazide. Weak for Reviewed, Deleted We do not suggest switching from hydrochlorothiazide to chlorthalidone or indapamide if the patient is adequately controlled on and tolerating hydrochlorothiazide. Weak against Reviewed, Deleted We suggest considering a switch from hydrochlorothiazide to chlorthalidone for patients whose hypertension is inadequately controlled on 50mg/day of hydrochlorothiazide. Weak for Reviewed, Deleted We recommend a dosage of 12.5-25mg/day of chlorthalidone, 25-50mg/day of hydrochlorothiazide, or a dosage of 2.5mg/day immediate-release or 1.5- 2.5mg/day sustained-release (not currently available in the US) of indapamide. Strong for Reviewed, Deleted We recommend using the following as alternative therapies for patients who cannot tolerate thiazide-type diuretics, as supplementary therapies for patients who do not reach their hypertensive goals, or for those starting on combination therapy: a. Angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers (but not together) b. Long-acting dihydropyridine calcium channel blockers (Modified from 2004 VA/DoD HTN CPG) Strong for Reviewed, New- replaced 2014 Recommendation Text 2014 Strength of Recommendation Recommendation Category Recommendation Section Number Page We recommend against the use of more than one of the following three drug classes together in the same patient: angiotensin- converting-enzyme inhibitors, angiotensin II receptor blockers, or direct renin inhibitors. Strong against Not reviewed, Not changed We recommend additional therapy in refractory hypertension (for those who do not tolerate or are not adequately controlled with triple therapy [i.e., thiazidetype diuretics, ACEI or ARB, and CCBs] described in Recommendation 43) or as supplementary therapy in some clinical indications. Drug classes for consideration can include (not in priority order): a. Aldosterone/mineralocorticoid receptor antagonists (e.g., spironolactone, eplerenone) b. Other potassium-sparing diuretic (i.e., amiloride) c. Alpha adrenergic blockers d. Beta adrenergic blockers e. Non-dihydropyridine calcium channel blockers f. Combined alpha-beta adrenergic blockers g. Peripherally acting antiadrenergic agents (reserpine, pending availability) h. Direct acting vasodilators (e.g., hydralazine, minoxidil) i. Centrally acting antiadrenergic drugs (e.g., clonidine, methyldopa) Strong for Reviewed, New- replaced We recommend against the use of alpha-adrenergic blockers as monotherapy, but this class of agents may be used as supplemental therapy or if warranted by comorbid conditions (e.g., symptomatic prostatic hypertrophy). (Modified from 2004 VA/DoD HTN CPG) Strong against Not reviewed, Deleted In patients with hypertension and chronic kidney disease (reduced kidney function with albuminuria), we recommend treatment with an angiotensin-converting enzyme inhibitor, or angiotensin II receptor blocker for improving kidney outcomes. (Modified from 2004 VA/DoD HTN CPG) Strong for Reviewed, Deleted In African American patients with hypertension, we recommend against using an angiotensin-converting-enzyme inhibitor or angiotensin II receptor blocker as monotherapy. Strong against Reviewed, Not changed 2014 Recommendation Text 2014 Strength of Recommendation Recommendation Category Recommendation Section Number Page In African American patients with hypertension and stage 1-3 chronic kidney disease, we suggest a combination of a thiazide-type diuretic (for cardiovascular protection) with either an angiotensin-converting- enzyme inhibitor or angiotensin II receptor blocker (for renal protection). Weak for Reviewed, Deleted Appendix E: Dietary Information Table E-1: Nutrient Composition of the Dietary Approaches to Stop Hypertension (DASH) Nutrient Recommended Intake Saturated fat 6% of total calories Total fat 27% of total calories Carbohydrate 55% of total calories Dietary fiber 30 grams/day Protein 18% of total calories Cholesterol 150 mg/day Total calories (energy) Balance energy intake and expenditure to maintain desirable body weight/prevent weight gain a Additional information on the DASH diet is available at: http://www.nhlbi.nih.gov/health/health-topics/topics/dash/.[159] b The DASH diet was shown to be most effective in lowering blood pressure when combined with sodium restriction.[124] Table E-2: Summary of Dietary Recommendations in the Mediterranean Dieta [132,160] Food Goal Recommended Olive oil 4 tbsp per day Tree nuts and peanuts 3 servings per week Fresh fruits including natural fruit juices 3 servings per day Vegetables 2 servings per day Seafood (primarily fatty fish) 3 servings per week Legumes 3 servings per week Sofritob 2 servings per week White meat In place of red meat Wine with meals 7 glasses per week, for those who drinkc Discouraged Soda drinks <1 drink per day Commercial baked goods, sweets, pastriesd <3 servings per week Spread fats <1 serving per day Red and processed meats <1 serving per day a Dietary patterns vary both within and among countries in the Mediterranean region, precluding a single standardized definition of the Mediterranean diet, though certain characteristic features are generally agreed upon by those studying its potential health effects; the table above represents the specific dietary recommendations used in the research study constituting our evidence base for this section of the guideline b Sofrito is a sauce made with tomato and onion, and often includes garlic, herbs, and olive oil c Recommended wine volume per glass: 100 mL for women, 150 mL for men d Commercial baked goods, sweets, and pastries included cakes, cookies, biscuits, and custard, and did not include those that are homemade Abbreviations: mL: milliliter; tbsp: tablespoon Appendix F: Drug Dosage Table Table F-1. Recommended Dosage for Selected Hypertension Drug Therapy Drug Usual Dose Range Commentsa Thiazide-type Diuretics Chlorthalidoneb HCTZb Indapamide 12.5-25 mg daily 25-50 mg dailyc IR: 2.5 mg daily May cause hyperuricemia/ gout Monitor K+ levels May cause photosensitivity (rare) May cause hyponatremia (1-2%) May be less effective in eGFR <30 mL/minute Angiotensin- Converting Enzyme Inhibitors (ACEI) Benazepril Enalapril Fosinopril Lisinoprilb Ramiprilb 10-40 mg/day (daily or divided bid) 5-40 mg/day (daily or divided bid) 10-40 mg daily 10-40 mg daily 2.5-20 mg/day (daily or divided bid) (10 mg daily for CV risk prevention) Avoid in women who are planning to become pregnant or who are pregnant; when pregnancy is contemplated or detected, discontinue as soon as possible, due to potential for fetal and neonatal morbidity and death; patients of child-bearing potential should also be educated about the risks Do not use if history of angioedema Avoid concomitant use of ACEI with ARB or direct renin inhibitor due to increased risk of hypotension, syncope, increased K+, and changes in kidney function (see Recommendation 26) Monitor K+ and kidney function; use caution if combined with, K+ sparing diuretic, or K+ supplement Consider interruption or discontinuation in patients who develop clinically significant decline in kidney function after initiation of therapy, until further work-up, as indicated (e.g., kidney artery stenosis) Compelling indications include: CKD with albuminuria (refer to VA/DoD CKD ); HFrEF; recent MI 1 See the VA/DoD Clinical Practice Guideline for the Management of Chronic Kidney Disease. Available at: https://www.healthquality.va.gov/guidelines/CD/CKD/ Drug Usual Dose Range Commentsa Angiotensin II Receptor Blockers (ARB) Azilsartand Candesartand Eprosartand Irbesartand Losartanb Olmesartand Telmisartand Valsartanb,e 40-80 mg daily (40 mg with diuretic) 8-32 mg daily 400-800 mg/daily (daily or divided bid) 75-300 mg daily 25-100 mg/day (daily or divided bid) 20-40 mg daily 20-80 mg daily 80-320 mg daily Avoid in women who are planning to become pregnant or who are pregnant; when pregnancy is contemplated or detected, discontinue as soon as possible; drugs that act directly on the renin angiotensin system can cause injury and death to the developing fetus; patients of child-bearing potential should also be educated about the risks Avoid concomitant use of ACEI with an ARB or direct renin inhibitor due to increased risk of hypotension, syncope, increased K+, and changes in kidney function (see Recommendation 26) In general, the lower doses should be considered in patients receiving diuretics Monitor K+ and kidney function; use caution if combined with, K+ sparing diuretic, or K+ supplement Consider interruption or discontinuation in patients who develop clinically significant decline in kidney function after initiation of therapy, until further work-up, as indicated (e.g., kidney artery stenosis) Compelling indications include: CKD with albuminuria (refer to VA/DoD CKD ); HFrEF; recent MI Long-Acting Calcium Channel Blockers (CCB) DHP CCBs Amlodipineb Felodipine Nifedipine sustained releaseb Non-DHP CCBs Verapamil sustained releaseb Diltiazem sustained releaseb 2.5-10 mg daily 2.5-10 mg daily 30-120 mg daily 120-480 mg divided daily- bid 120-540 mg daily Monitor AEs (DHP CCBs may cause ankle edema, dizziness, flushing, headache, constipation) Use with caution in patients with hepatic (CCBs) or kidney (non-DHP CCBs) dysfunction Non-DHP CCBs may be considered for rate control in supraventricular tachycardia or atrial fibrillation/flutter Verapamil may cause constipation; verapamil is contraindicated 2nd or 3rd degree AV block, severe LV dysfunction Diltiazem may decrease sinus rate; diltiazem is contraindicated in 2nd degree AV block; use with caution in LV dysfunction Verapamil or diltiazem should not usually be used with a beta-blocker due to risk of severe bradycardia or heart block 2 See the VA/DoD Clinical Practice Guideline for the Management of Chronic Kidney Disease. Available at: https://www.healthquality.va.gov/guidelines/CD/CKD/ Drug Usual Dose Range Commentsa Aldosterone/ Mineralocorticoid Receptor Antagonists Eplerenoned Spironolactoneb 50-100 mg/day (daily or divided bid) Avoid use if hyperkalemia or severe kidney dysfunction Monitor K+ and kidney function; consider risk vs. benefit if combined with ACEI, ARB, K+ sparing diuretic, or K+ supplement Higher risk of gynecomastia with spironolactone (9%) than eplerenone Compelling indications include: HFrEF Effective in resistant hypertension Other Potassium- Sparing Diuretics Amiloride 5-10 mg/daily Avoid use if hyperkalemia or severe kidney dysfunction Helpful in reducing hypokalemia caused by thiazide diuretics Effective in resistant hypertension Alpha-Adrenergic Blockers Doxazosin Prazosin Terazosinb 2-20 mg/day (divided bid or tid) 1-20 mg daily Initiate at low doses (1 mg) Administer 1st dose at bedtime to avoid syncope Avoid use as monotherapy May be considered for use in patients with symptomatic BPH Beta-Adrenergic Blockers Noncardioselective Propranolol Cardioselective Atenololb Metoprolol tartrateb Metoprolol succinate (XL)b Combined alpha- beta adrenergic blockers Carvedilol Labetalold Immediate release: 80-160 mg/day (divided bid) Sustained release: 80-160 mg daily 25-100 mg daily (adjust dose in CKD) Immediate release: 50-300 mg/day (daily or divided bid) Sustained release: Immediate releaseb : 12.5-50 mg/day (divided bid) Sustained released : 200-800 mg/day (divided bid) Discontinue with slow taper over one week Avoid combination with non-DHP CCB due to increased risk of bradycardia or heart attack As doses increase, cardioselectivity decreases Beta-blockers should be used cautiously in asthma Compelling indications include: HFrEF (evidence available for reduction in morbidity and mortality with bisoprolol, carvedilol, metoprolol succinate in HFrEF); recent MI; angina; rate control in atrial fibrillation/flutter; data available for select beta-blockers for migraine prevention Drug Usual Dose Range Commentsa Direct Acting Vasodilators Minoxidil Hydralazineb 2.5-100 mg/day (daily or divided bid) 50-200 mg/day (divided bid) Monitor for hypertrichosis, volume retention, and pericardial effusions with minoxidil Monitor for headache and SLE (dose- related) with hydralazine Direct acting vasodilators often require concomitant use of diuretic and beta- blocker to reduce edema and reflex tachycardia Centrally Acting Antiadrenergic Drugs Clonidine Tabletb Clonidine Patch Methyldopa 0.1-0.8 mg/day (divided bid) mg patch weekly (divided bid) Monitor for bradycardia, somnolence, and dry mouth. Taper dose to discontinue Clonidine patches may be useful in select patients May rarely cause bone marrow depression, positive Coombs test, hemolytic anemia and liver disorders (hepatitis, jaundice) a For complete drug information, review the manufacturer s prescribing information b DoD Basic Core Formulary item c HCTZ 12.5 mg may be considered as an initial dose with titration recommended to 25-50 mg daily; refer to Recommendation 25 and associated discussion for further information d Item not on VA National Formulary e Restricted to treatment of patients with systolic heart failure in VA Abbreviations: ACEI: angiotensin-converting enzyme inhibitor; AE: adverse effect; ARB: angiotensin II receptor blocker; AV: atrioventricular; bid: twice daily; BPH: benign prostatic hyperplasia; CCB: calcium channel blockers; CKD: chronic kidney disease; CV: cardiovascular; DHP: dihydropyridine; eGFR: estimated glomerular filtration rate; HCTZ: hydrochlorothiazide; HFrEF: heart failure with reduced ejection fraction; K+: potassium; LV: left ventricular; mL: milliliter; SLE: systemic lupus erythematosus; Appendix G: Guidance for Conducting Office Blood Pressure Measurement The following information has been adapted from the 2019 AHA Measurement of Blood Pressure in Properly prepare the patient Have the patient relax, sitting in a chair with feet flat on floor and back supported; the patient should be seated for 3-5 minutes without talking or moving around before recording the first blood pressure reading The patient should avoid caffeine, exercise, and smoking for at least 30 minutes before measurement Ensure that the patient has emptied his/her bladder Neither the patient nor the observer should talk during the rest period or during the measurement Remove clothing covering the location of cuff placement Measurements made while the patient is sitting on an examining table do not fulfill these criteria Use proper technique for blood pressure measurements Use an upper-arm cuff blood pressure measurement device that has been validated and ensure that the device is calibrated periodically Support the patient s arm (e.g., resting on a desk); the patient should not be holding his/her arm because isometric exercise will affect the blood pressure levels Position the middle of the cuff on the patient s upper arm at the level of the right atrium (midpoint of the sternum) Use the correct cuff size such that the bladder encircles 75%-100% of the arm Table G-1. Proper Blood Pressure Cuff Sizes Cuff Size Arm Circumference (cm) Bladder Dimension (width x length, cm) Abbreviation: cm: centimeter Take the proper measurements needed for diagnosis and treatment of elevated blood pressure/hypertension At the first visit, record blood pressure in both arms; use the arm that gives the higher reading for subsequent readings (if consistently 10-15 mm Hg higher) Separate repeated measurements by at least 30 seconds Properly document accurate blood pressure readings Record SBP and DBP Note the time that the most recent blood pressure medication was taken before measurements Use average the readings Use an average of 2 readings for the visit blood pressure For initial documentation of the patient s blood pressure, use an average of the visit blood pressures obtained on 2 occasions to estimate the individual s blood pressure Provide blood pressure readings to patient Provide patients their SBP/DBP readings both verbally and in writing; someone should help the patient interpret the results What is above should be common to each appropriate standardized office blood pressure measurement technique. The following are additional guidance specific for each technique: For fully automated office oscillometric manometer readings: Preprogram the manometer to wait five minutes before inflation begins and to take and average 2-3 readings at least 30 seconds apart; the most common intervals are 30 seconds, one minute, and two minutes Position the patient and place the proper sized cuff on the upper arm before initiating the wait time and blood pressure readings Turn the manometer on and set controls to take inflate to proper level (above sensed SBP) automatically and measure and average multiple readings; press the button to initiate wait period and automated readings (fully automated) Patient should remain quiet and not use electronic devices (e.g., phones) during the rest period and readings; person measuring the blood pressure may remain in the room (attended) or leave the patient alone in the room (unattended), but no one should interact or speak with the patient during the rest period and readings After the rest and measurements are completed, record the average blood pressure reading displayed; manometer should display the average of the 2-3 readings (as preset) For standard technique with automated oscillometric device: Use an upper-arm cuff oscillometric device that has been validated Position the patient and place the proper sized cuff on the upper arm before initiating the wait time and blood pressure readings Turn the manometer on and set controls to take/inflate to proper level (above sensed SBP) automatically Patient should remain quiet and not use electronic devices (e.g., phones), and no one should speak with the patient during the rest period and readings After the five-minute rest period, push the button to initiate the first inflation/reading; record SBP and DBP reading Take the next reading(s) with at least a 30 second interval between readings and record SBP and DBP readings displayed for each reading; record the average or median SBP and average or median DBP as the patient s blood pressure For standard auscultatory technique with manual manometer: Use an upper-arm cuff manual device that has been validated and recently calibrated; this includes a mercury manometer, an aneroid manometer, or an electronic manual non-oscillometric manometer for auscultatory determinations Position the patient and place the proper sized cuff on the upper arm before initiating the wait time and blood pressure readings Patient should remain quiet and not use electronic devices (e.g., phones), and no one should speak with the patient during the rest period and readings Use a palpated estimate of radial pulse obliteration pressure (disappearance or resumption of pulse when cuff is inflated/deflated) to estimate SBP; inflate the cuff 20-30 mm Hg above this level to perform the auscultatory determination of the blood pressure level Use either the stethoscope diaphragm or bell for auscultatory readings After the five-minute rest period, inflate the cuff and use auscultation to determine SBP and DBP; determine SBP and DBP as the onset of the first of at least two consecutive Korotkoff sounds (beats) and the last audible Korotkoff sound, respectively Record the SBP and DBP reading Take the next reading(s) with at least a 30 second interval between readings and record SBP and DBP readings for each reading; record the average or median SBP and average or median DBP as the patient s blood pressure Appendix H: Guidance for Conducting Home Blood Pressure Measurement The following information has been adapted from the 2019 AHA Measurement of Blood Pressure in Patient training provided by healthcare staff or providers: Provide information about hypertension diagnosis and treatment Provide information on the proper selection of a device Provide instruction on how patients can measure their own blood pressure (if possible, demonstrate the procedure or instruct how to access training video) Provide instruction that the HBPM device and blood pressure readings (log or electronic recording) should be brought to healthcare visits Provide education that individual blood pressure readings may vary greatly (high and low) across the monitoring period Preferred devices and cuffs: Use an upper-arm cuff oscillometric device that has been validated Use a device that is able to automatically store all readings, if possible Use a device that can print results or can send blood pressure values electronically to the healthcare provider, if possible Use a cuff that is appropriately sized for the patient s arm circumference Table H-1. Proper Blood Pressure Cuff Sizes Cuff Size Arm Circumference (cm) Bladder Dimension (width x length, cm) Abbreviation: cm: centimeter Best practices for the patient: Preparation Have an empty bladder Rest quietly in seated position with back supported (e.g., leaning back in chair) for at least five minutes Do not talk or text Position Sit with back supported Keep both feet flat on the floor Legs should not be crossed Blood pressure cuff should be placed on bare arm (not over clothes) Blood pressure cuff should be placed directly above the antecubital fossa (bend of the arm) Center of the bladder of the cuff (commonly marked on the cuff by the manufacturer) should be placed over the arterial pulsation of the patient s bare upper arm Cuff should be pulled taut, with comparable tightness at the top and bottom edges of the cuff, around the bare upper arm The arm with the cuff should be supported on a flat surface such as a table Number of readings Take two readings at least one minute apart in the morning before taking any antihypertensive medications and two readings at least one min apart in the evening before going to bed; some recommend only recording the second measurement Duration of monitoring Preferred monitoring period is 7 days (i.e., 28 readings or more scheduled readings); a minimum period of three days (i.e., 12 readings) may be sufficient, ideally in the period immediately before the next appointment with provider Monitoring conducted over consecutive days is ideal; however, readings taken on nonconsecutive days may also provide valid data Analyzing readings For each monitoring period, the average of all readings should be obtained Some guidelines and scientific statements recommend excluding the first day of readings; if the first day of readings is excluded, the minimum and preferred periods of HBPM should be four and eight days, respectively For a video developed for patients by the VA and DoD with instructions on measuring blood pressure at home, please visit https://www.healthquality.va.gov/guidelines/CD/htn/ and click on the Home Blood Pressure Monitoring video. Appendix I: Participant List Angela A. Allerman, PharmD, BPCS Formulary Management Branch, Pharmacy Operations Division, Defense Health Agency San Antonio, TX Jennifer Ballard-Hernandez, DNP, NP, CCRN VA Central Office Washington, DC Dan Berlowitz, MD, MPH Edith Nourse Rogers Memorial Veterans Hospital Bedford, MA William C. Cushman, MD Co-Chair, VA Hypertension-Lipid Field Advisory Committee Chief, Preventive Medicine Section VA Medical Center Memphis, TN Elaine Furmaga, PharmD National Clinical Pharmacy Program Manager VA Pharmacy Benefits Management Services Hines, IL Peter Glassman, MBBs, MSc, FACP Chair, Medical Advisory Panel, Pharmacy Benefit Management Services, Department of Veterans Affairs Washington, DC Elvira O. Gosmanova, MD, FASN Albany Stratton VA Medical Center Albany, NY CDR Travis E. Harrell, MD, FACC, FACP Naval Medical Center San Diego, Department of Cardiology San Diego, CA Asha Jain, MA, RD, CDE Outpatient Nutrition Services Clinical Dietitian Walter Reed National Military Medical Center Bethesda, MD Lillian Pinault, MS, RD, CSG, CDE Baltimore VA Medical Center Baltimore, MD Pedro Roldan, MD, FAAFP VA Greater Los Angeles Healthcare System Los Angeles, CA Lt Col Joseph C Sky, MD, FACP, FACC Travis Air Force Base Travis, CA Addison Taylor, MD, PhD Michael E. DeBakey VA Medical Center Houston, TX LTC Tommy L. Thompson, DNP, FNP-C Assistant Clinical Professor Family Nurse Practitioner and Women s Health Nurse Practitioner Program Madigan Army Medical Center Tacoma, WA CDR Mark P. Tschanz, DO, MACM, FACP Naval Medical Center San Diego San Diego, CA Lt Col Jesse Wickham, DO, FACP Brooke Army Medical Center San Antonio, TX Appendix J: Literature Review Search Terms and Strategy A. EMBASE and Medline Embase.com Syntax Question Set # Concept Strategy Questions and Diagnosis and Management #1 Blood pressure blood pressure /exp OR blood pressure monitoring /exp OR diastolic blood pressure /exp OR systolic blood pressure /exp OR systole /de OR diastole /de #2 'blood pressure':ti,ab OR 'systolic pressure*':ti,ab OR 'diastolic pressure*':ti,ab OR 'arterial pressure*':ti,ab OR bp:ti,ab #3 (systol*:ti,ab OR diastol*:ti,ab OR arterial:ti,ab OR sbp:ti,ab OR dbp:ti,ab) AND (pressure*:ti,ab OR mmhg:ti,ab OR 'mm hg':ti,ab) #5 BP measurement, screening, or monitoring #4 AND (monitor* OR measure* OR record* OR screen* OR test* OR evaluat* OR track*):ti,ab OR monitoring /exp OR measurement /exp OR screening/exp) #6 ('blood pressure'/exp AND 'hypertension'/exp/dm_dm,dm_pc,dm_th) OR 'blood pressure monitoring'/exp OR blood pressure monitor /exp OR blood pressure measurement /exp) #8 Interventions/BP methods #4 AND ('ambulatory blood pressure'/exp OR 'ambulatory blood pressure measurement'/exp OR ambulatory monitoring /exp OR home monitoring /exp OR self care /exp OR self monitoring /exp OR general practice /de OR health center /de) #9 #4 AND (routine OR office* OR clinic OR clinics OR general practice OR kiosk OR primary care OR auscultatory OR center OR centers OR traditional OR standard OR attended OR unattended):ti #10 #4 AND ((office NEAR/3 blood pressure ) OR (office NEAR/3 BP )) #11 #4 AND (automated OR wake OR self-measure* OR self-record* OR self NEAR/2 monitor* OR self NEAR/2 manag* OR home OR out-of- office OR out of office OR day* OR night* OR evening OR bedtime OR bed time OR morning* OR 24-hour OR 24-hour OR home blood pressure monitoring OR HBPM OR home BP OR ambulatory OR ABPM OR (ambulatory NEAR/3 blood pressure ) OR (ambulatory NEAR/3 BP) OR tele-monitoring OR telemonitoring) #12 #4 AND (sphygmomanomet* OR oscillomet* OR manometer /exp OR sphymomanometer /exp) #15 Test characteristics predictive validity /de OR predictive value /de OR prognosis /de OR sensitivity and specificity /de OR diagnostic accuracy OR diagnostic test accuracy study /exp OR diagnostic value /exp OR hypertension /mj/dm_di #16 Predict*:ti,ab OR Prognos*:ti,ab OR Sensitivity:ti,ab OR Specificity:ti,ab OR accuracy:ti,ab OR accurate:ti,ab #17 (sensitiv* OR accura* OR specific* OR reliab* OR predict* OR prognostic):ti,ab Question Set # Concept Strategy Questions and Diagnosis and Management (cont.) #19 Adherence and impact (Adhere* OR compliance OR comply OR goal OR goals OR threshold* OR achiev* OR benef* OR impact* OR improv* OR useful* OR utility):ti #20 adherence /exp OR patient compliance /exp OR treatment outcome /exp prehypertension 'hypertension'/exp OR 'hypertensive patient'/exp OR 'resistant hypertension'/exp OR 'masked hypertension'/exp OR 'white coat hypertension'/exp OR 'prehypertension'/exp #23 hypertension:ti,ab OR hypertensive:ti,ab OR 'borderline hypertensive':ti,ab OR prehyperten*:ti,ab OR 'white coat hypertension' OR wch OR 'masked hypertension' OR ((masked:ti,ab OR 'white coat':ti,ab OR borderline:ti,ab) AND hypertension:ti,ab) #24 (normal OR low OR high OR elevated OR borderline) NEAR/3 'blood pressure' #26 Combine BP and measure, screen, monitor, methods, accuracy #27 To diagnose and manage HTN #28 Combine BP and measure, screen, monitor, methods, adherence, and HTN Apply hedges below Questions and Non Pharmacological Interventions #1 hypertension 'hypertension'/exp OR 'hypertensive patient'/exp OR 'resistant hypertension'/exp OR 'masked hypertension'/exp OR 'white coat hypertension'/exp OR 'prehypertension'/exp #2 hypertension:ti,ab OR hypertensive:ti,ab OR 'borderline hypertensive':ti,ab OR (pre NEXT/1 hypertens*):ti,ab OR prehypertensi*:ti,ab OR 'white coat hypertension' OR wch OR 'masked hypertension' OR ((masked:ti,ab OR 'white coat':ti,ab OR borderline:ti,ab) AND hypertens*:ti,ab) #3 (high OR elevated OR borderline OR lower OR lowering) NEAR/3 'blood pressure' #5 'blood pressure'/exp OR 'diastolic blood pressure'/exp OR 'systolic blood pressure'/exp OR 'systole'/de OR 'diastole'/de #6 'blood pressure':ti,ab OR 'systolic pressure*':ti,ab OR 'diastolic pressure*':ti,ab OR 'arterial pressure*':ti,ab OR bp:ti,ab OR sbp:ti,ab OR dpb:ti,ab OR ((systol*:ti,ab OR diastol*:ti,ab OR arterial:ti,ab) AND (pressure*:ti,ab OR mmhg:ti,ab OR 'mm hg':ti,ab)) #8 Obesity 'obesity'/exp/mj OR 'obese patient'/exp/mj OR 'body mass'/exp OR 'body weight'/exp OR obese:ti OR obesity:ti OR overweight:ti Question Set # Concept Strategy Questions and Non Pharmacological Interventions (cont.) #9 General treatment of overweight/obesity with the aim of preventing/ controlling hypertension 'obesity'/exp/dm_dm,dm_dt,dm_su,dm_th AND 'hypertension'/exp/dm_dm,dm_pc,dm_th #10 Obesity - pharma 'obesity'/exp/dm_dt OR 'tetrahydrolipstatin'/exp OR 'lorcaserin'/exp OR 'phentermine plus topiramate'/exp OR 'liraglutide'/exp OR ('obesity'/exp AND (antihypertensives OR 'anti hypertensives' OR (antihypertensive NEAR/1 drug*) OR ('anti hypertensive' NEAR/1 drug*))) OR 'antiobesity agent'/exp OR 'amfebutamone plus naltrexone'/de #11 phentemine OR topiramate OR qsymia OR lorcaserin OR belviq OR orlistat OR xenical OR alli OR (naltrexone NEXT/1 bupropion) OR contrave OR liraglutide OR saxenda OR victoza OR phentermine OR benzphetamine OR phendimetrazine OR diethylpropion OR (antiobesity NEXT/1 agent*) OR (antiobesity NEXT/1 drug*) OR (obesity NEXT/1 agent*) OR (obesity NEXT/1 drug*) #13 Obesity - surgery 'bariatric surgery'/exp OR 'roux-en-y gastric bypass'/exp OR 'obesity'/exp/dm_su #14 (obes*:ti,ab OR bariatric:ti,ab OR gastric*:ti,ab OR stomach:ti,ab OR 'weight loss':ti,ab) AND surg*:ti,ab #15 obes*:ti AND (sleeve*:ti,ab OR lapband*:ti,ab OR band*:ti,ab OR 'gastric bypass':ti OR gastrectomy:ti,ab OR 'roux n y':ti,ab OR 'roux- en-y':ti,ab OR 'roux en y':ti,ab OR rygb:ti,ab) #17 Obesity lifestyle modification 'body weight loss'/exp OR (('eating habit'/exp OR 'diet therapy'/exp OR 'healthy lifestyle'/exp OR 'obesity management'/exp OR 'sedentary lifestyle'/exp OR 'lifestyle modification'/exp) AND 'body weight'/exp) #18 (eat*:ti OR habit*:ti OR diet*:ti OR lifestyle*:ti OR sedentary:ti OR activity:ti OR active:ti OR activities:ti OR exercise:ti) AND (change*:ti OR modif*:ti OR improve*:ti OR manag*:ti) #19 (weight:ti OR 'body mass':ti) AND (lose:ti OR loss:ti OR lost:ti OR lowering:ti OR reduc*:ti OR manag*:ti) OR ((weight:ti OR 'body mass':ti) AND (diet*:ti OR nutrition*:ti OR food*:ti) AND (prescription:ti OR prescribed:ti)) OR (dash AND diet) OR (mediterranean AND diet) OR 'dietary approach* to stop hypertension' OR 'dash diet':ti,ab OR 'dash diet'/exp OR ((diet* OR nutrition*):ti,ab AND (sodium OR salt OR potassium):ti,ab)) #20 (weight:ti OR 'body mass':ti) AND (lose:ti OR loss:ti OR lost:ti OR lowering:ti OR reduc*:ti OR manag*:ti) #21 'obesity'/exp/mj AND 'lifestyle modification'/exp OR ((diet*:ti OR nutrition*:ti) AND ('bp':ti OR 'blood pressure':ti OR 'hypertension':ti OR 'cardiovascular disease':ti OR 'cvd':ti)) #23 Combine Obesity AND Obesity pharma #24 Combine Obesity AND surgery Question Set # Concept Strategy Questions and Non Pharmacological Interventions (cont.) #25 Combine Obesity AND lifestyle mod #26 Combine final sets of Obesity 9 OR 23 OR 24 OR 25 #27 Physical activity 'exercise'/exp OR 'physical activity'/exp OR 'meditation'/exp OR 'transcendental meditation'/exp OR 'qigong'/exp OR 'qigong exercise'/exp OR 'tai chi'/exp OR 'yoga'/exp OR 'aerobic exercise'/exp OR 'physical activity, capacity and performance'/exp OR 'exercise intensity'/exp OR 'resistance training'/exp #28 exercise:ti,ab OR 'physical activity':ti,ab OR training:ti,ab OR isometric*:ti,ab OR 'weight training':ti,ab OR 'weight lift*':ti,ab OR 'resistance training':ti,ab OR walk* OR run* OR jog* OR stress*:ti,ab OR swim*:ti,ab OR aerobics OR (aerobic NEAR/3 exercis*) OR (aerobic NEAR/3 fitness) OR (aerobic NEAR/3 training) #29 qigong:ti,ab OR taichi:ti,ab OR 'tai chi':ti,ab OR yoga:ti,ab OR relax*:ti,ab OR meditat*:ti,ab #30 (exercise:ti OR ((physical NEAR/2 activity):ti)) AND (change*:ti OR improve*:ti OR modif*:ti OR increase*:ti) #31 sedentary:ti,ab OR 'sedentary lifestyle'/exp OR 'physical inactivity'/exp OR 'laziness'/exp #32 Combine final sets of physical activity #33 Combine HTN OR BP 4 OR 7 #34 Combine HTN OR BP with final obesity set #35 Combine HTN OR BP with final phys act set Apply hedges below Question Set # Concept Strategy Questions and Blood pressure thresholds and goals for pharmacologic interventions prehypertension. 