a case study of hypertension

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Clinical management and treatment decisions, hypertension in black americans, pharmacologic treatment of hypertension in black americans.

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Suzanne Oparil, Case study, American Journal of Hypertension , Volume 11, Issue S8, November 1998, Pages 192S–194S, https://doi.org/10.1016/S0895-7061(98)00195-2

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Ms. C is a 42-year-old black American woman with a 7-year history of hypertension first diagnosed during her last pregnancy. Her family history is positive for hypertension, with her mother dying at 56 years of age from hypertension-related cardiovascular disease (CVD). In addition, both her maternal and paternal grandparents had CVD.

At physician visit one, Ms. C presented with complaints of headache and general weakness. She reported that she has been taking many medications for her hypertension in the past, but stopped taking them because of the side effects. She could not recall the names of the medications. Currently she is taking 100 mg/day atenolol and 12.5 mg/day hydrochlorothiazide (HCTZ), which she admits to taking irregularly because “... they bother me, and I forget to renew my prescription.” Despite this antihypertensive regimen, her blood pressure remains elevated, ranging from 150 to 155/110 to 114 mm Hg. In addition, Ms. C admits that she has found it difficult to exercise, stop smoking, and change her eating habits. Findings from a complete history and physical assessment are unremarkable except for the presence of moderate obesity (5 ft 6 in., 150 lbs), minimal retinopathy, and a 25-year history of smoking approximately one pack of cigarettes per day. Initial laboratory data revealed serum sodium 138 mEq/L (135 to 147 mEq/L); potassium 3.4 mEq/L (3.5 to 5 mEq/L); blood urea nitrogen (BUN) 19 mg/dL (10 to 20 mg/dL); creatinine 0.9 mg/dL (0.35 to 0.93 mg/dL); calcium 9.8 mg/dL (8.8 to 10 mg/dL); total cholesterol 268 mg/dL (< 245 mg/dL); triglycerides 230 mg/dL (< 160 mg/dL); and fasting glucose 105 mg/dL (70 to 110 mg/dL). The patient refused a 24-h urine test.

Taking into account the past history of compliance irregularities and the need to take immediate action to lower this patient’s blood pressure, Ms. C’s pharmacologic regimen was changed to a trial of the angiotensin-converting enzyme (ACE) inhibitor enalapril, 5 mg/day; her HCTZ was discontinued. In addition, recommendations for smoking cessation, weight reduction, and diet modification were reviewed as recommended by the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). 1

After a 3-month trial of this treatment plan with escalation of the enalapril dose to 20 mg/day, the patient’s blood pressure remained uncontrolled. The patient’s medical status was reviewed, without notation of significant changes, and her antihypertensive therapy was modified. The ACE inhibitor was discontinued, and the patient was started on the angiotensin-II receptor blocker (ARB) losartan, 50 mg/day.

After 2 months of therapy with the ARB the patient experienced a modest, yet encouraging, reduction in blood pressure (140/100 mm Hg). Serum electrolyte laboratory values were within normal limits, and the physical assessment remained unchanged. The treatment plan was to continue the ARB and reevaluate the patient in 1 month. At that time, if blood pressure control remained marginal, low-dose HCTZ (12.5 mg/day) was to be added to the regimen.

Hypertension remains a significant health problem in the United States (US) despite recent advances in antihypertensive therapy. The role of hypertension as a risk factor for cardiovascular morbidity and mortality is well established. 2–7 The age-adjusted prevalence of hypertension in non-Hispanic black Americans is approximately 40% higher than in non-Hispanic whites. 8 Black Americans have an earlier onset of hypertension and greater incidence of stage 3 hypertension than whites, thereby raising the risk for hypertension-related target organ damage. 1 , 8 For example, hypertensive black Americans have a 320% greater incidence of hypertension-related end-stage renal disease (ESRD), 80% higher stroke mortality rate, and 50% higher CVD mortality rate, compared with that of the general population. 1 , 9 In addition, aging is associated with increases in the prevalence and severity of hypertension. 8

Research findings suggest that risk factors for coronary heart disease (CHD) and stroke, particularly the role of blood pressure, may be different for black American and white individuals. 10–12 Some studies indicate that effective treatment of hypertension in black Americans results in a decrease in the incidence of CVD to a level that is similar to that of nonblack American hypertensives. 13 , 14

Data also reveal differences between black American and white individuals in responsiveness to antihypertensive therapy. For instance, studies have shown that diuretics 15 , 16 and the calcium channel blocker diltiazem 16 , 17 are effective in lowering blood pressure in black American patients, whereas β-adrenergic receptor blockers and ACE inhibitors appear less effective. 15 , 16 In addition, recent studies indicate that ARB may also be effective in this patient population.

Angiotensin-II receptor blockers are a relatively new class of agents that are approved for the treatment of hypertension. Currently, four ARB have been approved by the US Food and Drug Administration (FDA): eprosartan, irbesartan, losartan, and valsartan. Recently, a 528-patient, 26-week study compared the efficacy of eprosartan (200 to 300 mg/twice daily) versus enalapril (5 to 20 mg/daily) in patients with essential hypertension (baseline sitting diastolic blood pressure [DBP] 95 to 114 mm Hg). After 3 to 5 weeks of placebo, patients were randomized to receive either eprosartan or enalapril. After 12 weeks of therapy within the titration phase, patients were supplemented with HCTZ as needed. In a prospectively defined subset analysis, black American patients in the eprosartan group (n = 21) achieved comparable reductions in DBP (−13.3 mm Hg with eprosartan; −12.4 mm Hg with enalapril) and greater reductions in systolic blood pressure (SBP) (−23.1 with eprosartan; −13.2 with enalapril), compared with black American patients in the enalapril group (n = 19) ( Fig. 1 ). 18 Additional trials enrolling more patients are clearly necessary, but this early experience with an ARB in black American patients is encouraging.

Efficacy of the angiotensin II receptor blocker eprosartan in black American with mild to moderate hypertension (baseline sitting DBP 95 to 114 mm Hg) in a 26-week study. Eprosartan, 200 to 300 mg twice daily (n = 21, solid bar), enalapril 5 to 20 mg daily (n = 19, diagonal bar). †10 of 21 eprosartan patients and seven of 19 enalapril patients also received HCTZ. Adapted from data in Levine: Subgroup analysis of black hypertensive patients treated with eprosartan or enalapril: results of a 26-week study, in Programs and abstracts from the 1st International Symposium on Angiotensin-II Antagonism, September 28–October 1, 1997, London, UK.

Approximately 30% of all deaths in hypertensive black American men and 20% of all deaths in hypertensive black American women are attributable to high blood pressure. Black Americans develop high blood pressure at an earlier age, and hypertension is more severe in every decade of life, compared with whites. As a result, black Americans have a 1.3 times greater rate of nonfatal stroke, a 1.8 times greater rate of fatal stroke, a 1.5 times greater rate of heart disease deaths, and a 5 times greater rate of ESRD when compared with whites. 19 Therefore, there is a need for aggressive antihypertensive treatment in this group. Newer, better tolerated antihypertensive drugs, which have the advantages of fewer adverse effects combined with greater antihypertensive efficacy, may be of great benefit to this patient population.

1. Joint National Committee : The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure . Arch Intern Med 1997 ; 24 157 : 2413 – 2446 .

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4. Pooling Project Research Group : Relationship of blood pressure, serum cholesterol, smoking habit, relative weight and ECG abnormalities to the incidence of major coronary events: Final report of the pooling project . J Chronic Dis 1978 ; 31 : 201 – 306 .

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9. Klag MJ , Whelton PK , Randall BL et al.  : End-stage renal disease in African-American and white men: 16-year MRFIT findings . JAMA 1997 ; 277 : 1293 – 1298 .

10. Neaton JD , Kuller LH , Wentworth D et al.  : Total and cardiovascular mortality in relation to cigarette smoking, serum cholesterol concentration, and diastolic blood pressure among black and white males followed up for five years . Am Heart J 1984 ; 3 : 759 – 769 .

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13. Hypertension Detection and Follow-up Program Cooperative Group : Five-year findings of the Hypertension Detection and Follow-up Program: mortality by race-sex and blood pressure level: a further analysis . J Community Health 1984 ; 9 : 314 – 327 .

14. Ooi WL , Budner NS , Cohen H et al.  : Impact of race on treatment response and cardiovascular disease among hypertensives . Hypertension 1989 ; 14 : 227 – 234 .

15. Weinberger MH : Racial differences in antihypertensive therapy: evidence and implications . Cardiovasc Drugs Ther 1990 ; 4 ( suppl 2 ): 379 – 392 .

16. Materson BJ , Reda DJ , Cushman WC et al.  : Single-drug therapy for hypertension in men: A comparison of six antihypertensive agents with placebo . N Engl J Med 1993 ; 328 : 914 – 921 .

17. Materson BJ , Reda DJ , Cushman WC for the Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents : Department of Veterans Affairs single-drug therapy of hypertension study: Revised figures and new data . Am J Hypertens 1995 ; 8 : 189 – 192 .

18. Levine B : Subgroup analysis of black hypertensive patients treated with eprosartan or enalapril: results of a 26-week study , in Programs and abstracts from the first International Symposium on Angiotensin-II Antagonism , September 28 – October 1 , 1997 , London, UK .

19. American Heart Association: 1997 Heart and Stroke Statistical Update . American Heart Association , Dallas , 1997 .

• hypertension
• blood pressure
• african american

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Newly diagnosed hypertension: case study

Angela Brown

Trainee Advanced Nurse Practitioner, East Belfast GP Federation, Northern Ireland

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The role of an advanced nurse practitioner encompasses the assessment, diagnosis and treatment of a range of conditions. This case study presents a patient with newly diagnosed hypertension. It demonstrates effective history taking, physical examination, differential diagnoses and the shared decision making which occurred between the patient and the professional. It is widely acknowledged that adherence to medications is poor in long-term conditions, such as hypertension, but using a concordant approach in practice can optimise patient outcomes. This case study outlines a concordant approach to consultations in clinical practice which can enhance adherence in long-term conditions.

Hypertension is a worldwide problem with substantial consequences ( Fisher and Curfman, 2018 ). It is a progressive condition ( Jamison, 2006 ) requiring lifelong management with pharmacological treatments and lifestyle adjustments. However, adopting these lifestyle changes can be notoriously difficult to implement and sustain ( Fisher and Curfman, 2018 ) and non-adherence to chronic medication regimens is extremely common ( Abegaz et al, 2017 ). This is also recognised by the National Institute for Health and Care Excellence (NICE) (2009) which estimates that between 33.3% and 50% of medications are not taken as recommended. Abegaz et al (2017) furthered this by claiming 83.7% of people with uncontrolled hypertension do not take medications as prescribed. However, leaving hypertension untreated or uncontrolled is the single largest cause of cardiovascular disease ( Fisher and Curfman, 2018 ). Therefore, better adherence to medications is associated with better outcomes ( World Health Organization, 2003 ) in terms of reducing the financial burden associated with the disease process on the health service, improving outcomes for patients ( Chakrabarti, 2014 ) and increasing job satisfaction for professionals ( McKinnon, 2013 ). Therefore, at a time when growing numbers of patients are presenting with hypertension, health professionals must adopt a concordant approach from the initial consultation to optimise adherence.

Great emphasis is placed on optimising adherence to medications ( NICE, 2009 ), but the meaning of the term ‘adherence’ is not clear and it is sometimes used interchangeably with compliance and concordance ( De Mauri et al, 2022 ), although they are not synonyms. Compliance is an outdated term alluding to paternalism, obedience and passivity from the patient ( Rae, 2021 ), whereby the patient's behaviour must conform to the health professional's recommendations. Adherence is defined as ‘the extent to which a person's behaviour, taking medication, following a diet and/or executing lifestyle changes, corresponds with agreed recommendations from a health care provider’ ( Chakrabarti, 2014 ). This term is preferred over compliance as it is less paternalistic ( Rae, 2021 ), as the patient is included in the decision-making process and has agreed to the treatment plan. While it is not yet widely embraced or used in practice ( Fawcett, 2020 ), concordance is recognised, not as a behaviour ( Rae, 2021 ) but more an approach or method which focuses on the equal partnership between patient and professional ( McKinnon, 2013 ) and enables effective and agreed treatment plans.

NICE last reviewed its guidance on medication adherence in 2019 and did not replace adherence with concordance within this. This supports the theory that adherence is an outcome of good concordance and the two are not synonyms. NICE (2009) guidelines, which are still valid, show evidence of concordant principles to maximise adherence. Integrating the theoretical principles of concordance into this case study demonstrates how the trainee advanced nurse practitioner aimed to individualise patient-centred care and improve health outcomes through optimising adherence.

Patient introduction and assessment

Jane (a pseudonym has been used to protect the patient's anonymity; Nursing and Midwifery Council (NMC) 2018 ), is a 45-year-old woman who had been referred to the surgery following an attendance at an emergency department. Jane had been role-playing as a patient as part of a teaching session for health professionals when it was noted that her blood pressure was significantly elevated at 170/88 mmHg. She had no other symptoms. Following an initial assessment at the emergency department, Jane was advised to contact her GP surgery for review and follow up. Nazarko (2021) recognised that it is common for individuals with high blood pressure to be asymptomatic, contributing to this being referred to as the ‘silent killer’. Hypertension is generally only detected through opportunistic checking of blood pressure, as seen in Jane's case, which is why adults over the age of 40 years are offered a blood pressure check every 5 years ( Bostock-Cox, 2013 ).

Consultation

Jane presented for a consultation at the surgery. Green (2015) advocates using a model to provide a structured approach to consultations which ensures quality and safety, and improves time management. Young et al (2009) claimed that no single consultation model is perfect, and Diamond-Fox (2021) suggested that, with experience, professionals can combine models to optimise consultation outcomes. Therefore, to effectively consult with Jane and to adapt to her individual personality, different models were intertwined to provide better person-centred care.

The Calgary–Cambridge model is the only consultation model that places emphasis on initiating the session, despite it being recognised that if a consultation gets off to a bad start this can interfere throughout ( Young et al, 2009 ). Being prepared for the consultation is key. Before Jane's consultation, the environment was checked to minimise interruptions, ensuring privacy and dignity ( Green, 2015 ; NMC, 2018 ), the seating arrangements optimised to aid good body language and communication ( Diamond-Fox, 2021 ) and her records were viewed to give some background information to help set the scene and develop a rapport ( Young et al, 2009 ). Being adequately prepared builds the patient's trust and confidence in the professional ( Donnelly and Martin, 2016 ) but equally viewing patient information can lead to the professional forming preconceived ideas ( Donnelly and Martin, 2016 ). Therefore, care was taken by the trainee advanced nurse practitioner to remain open-minded.

During Jane's consultation, a thorough clinical history was taken ( Table 1 ). History taking is common to all consultation models and involves gathering important information ( Diamond-Fox, 2021 ). History-taking needs to be an effective ( Bostock-Cox, 2019 ), holistic process ( Harper and Ajao, 2010 ) in order to be thorough, safe ( Diamond-Fox, 2021 ) and aid in an accurate diagnosis. The key skill for taking history is listening and observing the patient ( Harper and Ajao, 2010 ). Sir William Osler said:‘listen to the patient as they are telling you the diagnosis’, but Knott and Tidy (2021) suggested that patients are barely given 20 seconds before being interrupted, after which they withdraw and do not offer any new information ( Demosthenous, 2017 ). Using this guidance, Jane was given the ‘golden minute’ allowing her to tell her ‘story’ without being interrupted ( Green, 2015 ). This not only showed respect ( Ingram, 2017 ) but interest in the patient and their concerns.

Once Jane shared her story, it was important for the trainee advanced nurse practitioner to guide the questioning ( Green 2015 ). This was achieved using a structured approach to take Jane's history, which optimised efficiency and effectiveness, and ensured that pertinent information was not omitted ( Young et al, 2009 ). Thomas and Monaghan (2014) set out clear headings for this purpose. These included:

• The presenting complaint
• Past medical history
• Drug history
• Social history
• Family history.

McPhillips et al (2021) also emphasised a need for a systemic enquiry of the other body systems to ensure nothing is missed. From taking this history it was discovered that Jane had been feeling well with no associated symptoms or red flags. A blood pressure reading showed that her blood pressure was elevated. Jane had no past medical history or allergies. She was not taking any medications, including prescribed, over the counter, herbal or recreational. Jane confirmed that she did not drink alcohol or smoke. There was no family history to note, which is important to clarify as a genetic link to hypertension could account for 30–50% of cases ( Nazarko, 2021 ). The information gathered was summarised back to Jane, showing good practice ( McPhillips et al, 2021 ), and Jane was able to clarify salient or missing points. Green (2015) suggested that optimising the patient's involvement in this way in the consultation makes her feel listened to which enhances patient satisfaction, develops a therapeutic relationship and demonstrates concordance.

During history taking it is important to explore the patient's ideas, concerns and expectations. Moulton (2007) refers to these as the ‘holy trinity’ and central to upholding person-centredness ( Matthys et al, 2009 ). Giving Jane time to discuss her ideas, concerns and expectations allowed the trainee advanced nurse practitioner to understand that she was concerned about her risk of a stroke and heart attack, and worried about the implications of hypertension on her already stressful job. Using ideas, concerns and expectations helped to understand Jane's experience, attitudes and perceptions, which ultimately will impact on her health behaviours and whether engagement in treatment options is likely ( James and Holloway, 2020 ). Establishing Jane's views demonstrated that she was eager to engage and manage her blood pressure more effectively.

Vincer and Kaufman (2017) demonstrated, through their case study, that a failure to ask their patient's viewpoint at the initial consultation meant a delay in engagement with treatment. They recognised that this delay could have been avoided with the use of additional strategies had ideas, concerns and expectations been implemented. Failure to implement ideas, concerns and expectations is also associated with reattendance or the patient seeking second opinions ( Green, 2015 ) but more positively, when ideas, concerns and expectations is implemented, it can reduce the number of prescriptions while sustaining patient satisfaction ( Matthys et al, 2009 ).

Physical examination

Once a comprehensive history was taken, a physical examination was undertaken to supplement this information ( Nuttall and Rutt-Howard, 2016 ). A physical examination of all the body systems is not required ( Diamond-Fox, 2021 ) as this would be extremely time consuming, but the trainee advanced nurse practitioner needed to carefully select which systems to examine and use good examination technique to yield a correct diagnosis ( Knott and Tidy, 2021 ). With informed consent, clinical observations were recorded along with a full cardiovascular examination. The only abnormality discovered was Jane's blood pressure which was 164/90 mmHg, which could suggest stage 2 hypertension ( NICE, 2019 ; 2022 ). However, it is the trainee advanced nurse practitioner's role to use a hypothetico-deductive approach to arrive at a diagnosis. This requires synthesising all the information from the history taking and physical examination to formulate differential diagnoses ( Green, 2015 ) from which to confirm or refute before arriving at a final diagnosis ( Barratt, 2018 ).

Differential diagnosis

Hypertension can be triggered by secondary causes such as certain drugs (non-steroidal anti-inflammatory drugs, steroids, decongestants, sodium-containing medications or combined oral contraception), foods (liquorice, alcohol or caffeine; Jamison, 2006 ), physiological response (pain, anxiety or stress) or pre-eclampsia ( Jamison, 2006 ; Schroeder, 2017 ). However, Jane had clarified that these were not contributing factors. Other potential differentials which could not be ruled out were the white-coat syndrome, renal disease or hyperthyroidism ( Schroeder, 2017 ). Further tests were required, which included bloods, urine albumin creatinine ratio, electrocardiogram and home blood pressure monitoring, to ensure a correct diagnosis and identify any target organ damage.

Joint decision making

At this point, the trainee advanced nurse practitioner needed to share their knowledge in a meaningful way to enable the patient to participate with and be involved in making decisions about their care ( Rostoft et al, 2021 ). Not all patients wish to be involved in decision making ( Hobden, 2006 ) and this must be respected ( NMC, 2018 ). However, engaging patients in partnership working improves health outcomes ( McKinnon, 2013 ). Explaining the options available requires skill so as not to make the professional seem incompetent and to ensure the patient continues to feel safe ( Rostoft et al, 2021 ).

Information supported by the NICE guidelines was shared with Jane. These guidelines advocated that in order to confirm a diagnosis of hypertension, a clinic blood pressure reading of 140/90 mmHg or higher was required, with either an ambulatory or home blood pressure monitoring result of 135/85 mmHg or higher ( NICE, 2019 ; 2022 ). However, the results from a new retrospective study suggested that the use of home blood pressure monitoring is failing to detect ‘non-dippers’ or ‘reverse dippers’ ( Armitage et al, 2023 ). These are patients whose blood pressure fails to fall during their nighttime sleep. This places them at greater risk of cardiovascular disease and misdiagnosis if home blood pressure monitors are used, but ambulatory blood pressure monitors are less frequently used in primary care and therefore home blood pressure monitors appear to be the new norm ( Armitage et al, 2023 ).

Having discussed this with Jane she was keen to engage with home blood pressure monitoring in order to confirm the potential diagnosis, as starting a medication without a true diagnosis of hypertension could potentially cause harm ( Jamison, 2006 ). An accurate blood pressure measurement is needed to prevent misdiagnosis and unnecessary therapy ( Jamison, 2006 ) and this is dependent on reliable and calibrated equipment and competency in performing the task ( Bostock-Cox, 2013 ). Therefore, Jane was given education and training to ensure the validity and reliability of her blood pressure readings.

For Jane, this consultation was the ideal time to offer health promotion advice ( Green, 2015 ) as she was particularly worried about her elevated blood pressure. Offering health promotion advice is a way of caring, showing support and empowerment ( Ingram, 2017 ). Therefore, Jane was provided with information on a healthy diet, the reduction of salt intake, weight loss, exercise and continuing to abstain from smoking and alcohol ( Williams, 2013 ). These were all modifiable factors which Jane could implement straight away to reduce her blood pressure.

Safety netting

The final stage and bringing this consultation to a close was based on the fourth stage of Neighbour's (1987) model, which is safety netting. Safety netting identifies appropriate follow up and gives details to the patient on what to do if their condition changes ( Weiss, 2019 ). It is important that the patient knows who to contact and when ( Young et al, 2009 ). Therefore, Jane was advised that, should she develop chest pains, shortness of breath, peripheral oedema, reduced urinary output, headaches, visual disturbances or retinal haemorrhages ( Schroeder, 2017 ), she should present immediately to the emergency department, otherwise she would be reviewed in the surgery in 1 week.

Jane was followed up in a second consultation 1 week later with her home blood pressure readings. The average reading from the previous 6 days was calculated ( Bostock-Cox, 2013 ) and Jane's home blood pressure reading was 158/82 mmHg. This reading ruled out white-coat syndrome as Jane's blood pressure remained elevated outside clinic conditions (white-coat syndrome is defined as a difference of more than 20/10 mmHg between clinic blood pressure readings and the average home blood pressure reading; NICE, 2019 ; 2022 ). Subsequently, Jane was diagnosed with stage 2 essential (or primary) hypertension. Stage 2 is defined as a clinic blood pressure of 160/100 mmHg or higher or a home blood pressure of 150/95 mmHg or higher ( NICE, 2019 ; 2022 ).

A diagnosis of hypertension can be difficult for patients as they obtain a ‘sick label’ despite feeling well ( Jamison, 2006 ). This is recognised as a deterrent for their motivation to initiate drug treatment and lifestyle changes ( Williams, 2013 ), presenting a greater challenge to health professionals, which can be addressed through concordance strategies. However, having taken Jane's bloods, electrocardiogram and urine albumin:creatinine ratio in the first consultation, it was evident that there was no target organ damage and her Qrisk3 score was calculated as 3.4%. These results provided reassurance for Jane, but she was keen to engage and prevent any potential complications.

Agreeing treatment

Concordance is only truly practised when the patient's perspectives are valued, shared and used to inform planning ( McKinnon, 2013 ). The trainee advanced nurse practitioner now needed to use the information gained from the consultations to formulate a co-produced and meaningful treatment plan based on the best available evidence ( Diamond-Fox and Bone, 2021 ). Jane understood the risk associated with high blood pressure and was keen to begin medication as soon as possible. NICE guidelines ( 2019 ; 2022 ) advocate the use of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blockers in patients under 55 years of age and not of Black African or African-Caribbean origin. However, ACE inhibitors seem to be used as the first-line treatment for hypertensive patients under the age of 55 years ( O'Donovan, 2019 ).

ACE inhibitors directly affect the renin–angiotensin-aldosterone system which plays a central role in regulation of blood pressure ( Porth, 2015 ). Renin is secreted by the juxtaglomerular cells, in the kidneys' nephrons, when there is a decrease in renal perfusion and stimulation of the sympathetic nervous system ( O'Donovan, 2018 ). Renin then combines with angiotensinogen, a circulating plasma globulin from the liver, to form angiotensin I ( Kumar and Clark, 2017 ). Angiotensin I is inactive but, through ACE, an enzyme present in the endothelium of the lungs, it is transformed into angiotensin II ( Kumar and Clark, 2017 ). Angiotensin II is a vasoconstrictor which increases vascular resistance and in turn blood pressure ( Porth, 2015 ) while also stimulating the adrenal gland to produce aldosterone. Aldosterone reduces sodium excretion in the kidneys, thus increasing water reabsorption and therefore blood volume ( Porth, 2015 ). Using an ACE inhibitor prevents angiotensin II formation, which prevents vasoconstriction and stops reabsorption of sodium and water, thus reducing blood pressure.

When any new medication is being considered, providing education is key. This must include what the medication is for, the importance of taking it, any contraindications or interactions with the current medications being taken by the patient and the potential risk of adverse effects ( O'Donovan, 2018 ). Sharing this information with Jane allowed her to weigh up the pros and cons and make an informed choice leading to the creation of an individualised treatment plan.

Jamison (2006) placed great emphasis on sharing information about adverse effects, because patients with hypertension feel well before commencing medications, but taking medication has the potential to cause side effects which can affect adherence. Therefore, the range of side effects were discussed with Jane. These include a persistent, dry non-productive cough, hypotension, hypersensitivity, angioedema and renal impairment with hyperkalaemia ( Hitchings et al, 2019 ). ACE inhibitors have a range of adverse effects and most resolve when treatment is stopped ( Waterfield, 2008 ).

Following discussion with Jane, she proceeded with taking an ACE inhibitor and was encouraged to report any side effects in order to find another more suitable medication and to prevent her hypertension from going untreated. This information was provided verbally and written which is seen as good practice ( Green, 2015 ). Jane was followed up with fortnightly blood pressure recordings and urea and electrolyte checks and her dose of ramipril was increased fortnightly until her blood pressure was under 140/90 mmHg ( NICE, 2019 ; 2022 ).

Conclusions

Adherence to medications can be difficult to establish and maintain, especially for patients with long-term conditions. This can be particularly challenging for patients with hypertension because they are generally asymptomatic, yet acquire a sick label and start lifelong medication and lifestyle adjustments to prevent complications. Through adopting a concordant approach in practice, the outcome of adherence can be increased. This case study demonstrates how concordant strategies were implemented throughout the consultation to create a therapeutic patient–professional relationship. This optimised the creation of an individualised treatment plan which the patient engaged with and adhered to.

• Hypertension is a growing worldwide problem
• Appropriate clinical assessment, diagnosis and management is key to prevent misdiagnosis
• Long-term conditions are associated with high levels of non-adherence to treatments
• Adopting a concordance approach to practice optimises adherence and promotes positive patient outcomes

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• Super-response to renal denervation in treatment-resistant essential hypertension
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• http://orcid.org/0000-0002-4232-7146 Nawaz Z Safdar 1 , 2 ,
• http://orcid.org/0000-0002-5034-064X Muhammad Usman Shah 3 , 4 ,
• Ali Ali 3 and
• Syed Yaseen Naqvi 3
• 1 Department of Internal Medicine , Pennsylvania Hospital , Philadelphia , Pennsylvania , USA
• 2 Department of Internal Medicine , Leeds Teaching Hospitals NHS Trust , Leeds , UK
• 3 Department of Cardiology , Hull University Teaching Hospitals NHS Trust , Hull , UK
• 4 University of Lincoln , Lincoln , UK
• Correspondence to Dr Muhammad Usman Shah; usmanshah44{at}gmail.com

Renal denervation may be indicated in patients with treatment-resistant essential hypertension to decrease sympathetic nervous activity and optimise blood pressure. We present the case of a woman in her 50s with long-standing essential hypertension, a previous transient ischaemic attack, obesity and a family history of cardiovascular disease, who presented with persistent 24-hour ambulatory hypertension despite ongoing lifestyle modifications and being on five antihypertensive agents with no evidence of an alternative primary aetiology. She had intermittent palpitations and blurring of vision alongside evidence of left ventricular hypertrophy on a CT scan. She underwent renal denervation, following which, not only was she able to cease all antihypertensive therapy but managed to maintain optimised blood pressure with subsequent reversal of left ventricular hypertrophy. Trials have demonstrated modest but inconsistent reductions in blood pressure whereas our case represents a ‘super-response’ likely due to a higher number of circumferential ablations in comparison to previous studies.

• Hypertension
• Interventional cardiology
• Renal intervention

https://doi.org/10.1136/bcr-2024-260945

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Contributors The following authors were responsible for drafting of the text, sourcing and editing of clinical images, investigation results, drawing original diagrams and algorithms, and critical revision for important intellectual content: NZS, MUS, AA and SYN. The following authors gave final approval of the manuscript: MUS and SYN.

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.

Competing interests None declared.

Provenance and peer review Not commissioned; externally peer reviewed.

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Risk factors of undiagnosed and uncontrolled hypertension in primary care patients with hypertension: a cross-sectional study

Affiliations.

• 1 Department of Family and Preventive Medicine, University of Utah, Salt Lake City, UT, USA.
• 2 Utah Department of Health and Human Services, Salt Lake City, UT, USA.
• 3 Intermountain Healthcare, Salt Lake City, UT, USA.
• 4 Department of Family and Preventive Medicine, University of Utah, Salt Lake City, UT, USA. [email protected].
• 5 Faculty of Health and Healthcare Sciences, Westsächsische Hochschule Zwickau, Kornmarkt 1, 08056 Zwickau, 08012, Zwickau, Saxony, Germany. [email protected].
• PMID: 39164618
• PMCID: PMC11334361
• DOI: 10.1186/s12875-024-02511-4

Background: Hypertension is a common heart condition in the United States (US) and severely impacts racial and ethnic minority populations. While the understanding of hypertension has grown considerably, there remain gaps in US healthcare research. Specifically, there is a lack of focus on undiagnosed and uncontrolled hypertension in primary care settings.

Aim: The present study investigates factors associated with undiagnosed and uncontrolled hypertension in primary care patients with hypertension. The study also examines whether Black/African Americans are at higher odds of undiagnosed and uncontrolled hypertension compared to White patients.

Methods: A cross-sectional study was conducted using electronic health records (EHR) data from the University of Utah primary care health system. The study included for analysis 24,915 patients with hypertension who had a primary care visit from January 2020 to December 2020. Multivariate logistic regression assessed the odds of undiagnosed and uncontrolled hypertension.

Results: Among 24,915 patients with hypertension, 28.6% (n = 7,124) were undiagnosed and 37.4% (n = 9,319) were uncontrolled. Factors associated with higher odds of undiagnosed hypertension included age 18-44 (2.05 [1.90-2.21]), Hispanic/Latino ethnicity (1.13 [1.03-1.23]), Medicaid (1.43 [1.29-1.58]) or self-pay (1.32 [1.13-1.53]) insurance, CCI 1-2 (1.79 [1.67-1.92]), and LDL-c ≥ 190 mg/dl (3.05 [1.41-6.59]). For uncontrolled hypertension, risk factors included age 65+ (1.11 [1.08-1.34]), male (1.24 [1.17-1.31]), Native-Hawaiian/Pacific Islander (1.32 [1.05-1.62]) or Black/African American race (1.24 [1.11-1.57]) , and self-pay insurance (1.11 [1.03-1.22]).

Conclusion: The results of this study suggest that undiagnosed and uncontrolled hypertension is prevalent in primary care. Critical risk factors for undiagnosed hypertension include younger age, Hispanic/Latino ethnicity, very high LDL-c, low comorbidity scores, and self-pay or medicaid insurance. For uncontrolled hypertension, geriatric populations, males, Native Hawaiian/Pacific Islanders, and Black/African Americans, continue to experience greater burdens than their counterparts. Substantial efforts are needed to strengthen hypertension diagnosis and to develop tailored hypertension management programs in primary care, focusing on these populations.

Keywords: Black/African americans; Native Hawaiian/Pacific Islander; Primary care; Uncontrolled hypertension; Undiagnosed hypertension.

© 2024. The Author(s).

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Conflict of interest statement

The authors declare no competing interests.

Flow chart of included data

Forest plot of significant risk…

Forest plot of significant risk factors of undiagnosed hypertension

Forest plot of significant risk factors of undiagnosed hypertension: Black/African Americans vs. White

Forest plot of significant risk factors of uncontrolled hypertension

Forest plot of significant risk factors of uncontrolled hypertension: Black/African Americans vs. White

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• Published: 06 September 2024

Home blood pressure measurement and hypertension control according to the length of antihypertensive treatment among employees

• Yukako Tatsumi 1 , 2 ,
• Azusa Shima 2 , 3 ,
• Michihiro Satoh 4 , 5 ,
• Ayumi Morino 2 , 3 ,
• Yuichiro Kawatsu 3 ,
• Kei Asayama 1 ,
• Naomi Miyamatsu 2 &
• Takayoshi Ohkubo 1  

Hypertension Research ( 2024 ) Cite this article

Metrics details

This study aimed to investigate the association between the frequency of home blood pressure (HBP) measurement and hypertension control in a middle-aged working population. This study included 627 employees aged 40 years or older who underwent health check-ups for 2 consecutive years from 2019 to 2022 and had blood pressure (BP) ≥ 140/90 mmHg at the health check-up in the first year. The participants were stratified by the length of antihypertensive treatment (within 1 year, >1 year) using data in the first and second years, and were classified by the frequency of HBP measurement (<6 times/week, almost every day) using data in the second year. In each treatment length, logistic regression analyses were used to estimate multivariable adjusted odds ratios (ORs) of controlled hypertension (BP at health check-ups <140/90 mmHg in the second year) in those who measured HBP almost every day compared with those who measured HBP < 6 times/week. The ORs (95% confidence intervals) were 1.56 (0.94–2.73) in those within 1 year of starting treatment and 0.74 (0.44–1.22) in those with more than 1 year of starting treatment. In participants with BP ≥ 160/100 mmHg in the first year, the corresponding ORs were 1.94 (1.04–3.64) and 0.41 (0.13–1.23), respectively. In conclusion, in individuals within 1 year of starting treatment, those who measure HBP almost every day tend to have good control of hypertension. In particular, in those who have BP ≥ 160/100 mmHg before starting antihypertensive medication, measuring HBP almost every day is associated with good control of hypertension.

Among those within 1 year of starting the treatment (Group1) especially in those with blood pressure ≥160/100 mmHg, the frequency of home blood pressure measurement was associated with hypertension control. It was not associated among those with more than 1 year of starting the treatment (Group 2).

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Acknowledgements

We thank all members of Heiwado Health Insurance Society and Heiwado Occupational Health Care Office, especially Ms. Atsuko Kawamura for her careful coordination of the staff who administered the health check-ups and Mr. Shinobu Takada for his contribution to collecting the data. This study was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (21K17313 and 21K19670).

This study was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (21K17313, 21K19670, and 22H03358).

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Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan

Yukako Tatsumi, Kei Asayama & Takayoshi Ohkubo

Department of Clinical Nursing, Shiga University of Medical Science, Shiga, Japan

Yukako Tatsumi, Azusa Shima, Ayumi Morino & Naomi Miyamatsu

Occupational Health Care Office, HEIWADO CO., LTD., Shiga, Japan

Azusa Shima, Ayumi Morino & Yuichiro Kawatsu

Division of Public Health, Hygiene and Epidemiology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan

Michihiro Satoh

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Three of the authors (AS, AM, and YK) are health professionals of the retail company whose employees are insured by the Employees’ Health Insurance Society. They provided the data for the present study. The other authors do not have any conflict of interest to disclose.

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Tatsumi, Y., Shima, A., Satoh, M. et al. Home blood pressure measurement and hypertension control according to the length of antihypertensive treatment among employees. Hypertens Res (2024). https://doi.org/10.1038/s41440-024-01863-9

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Case 1: Management of Hypertensive Encephalopathy

A 45-year-old man with a 2-month history of progressive headache presented to the emergency department with nausea, vomiting, visual disturbance, and confusion for 1 day. He denied fever, weakness, numbness, shortness of breath, and flulike symptoms. He had significant medical history of hypertension and was on a β-blocker in the past, but a year ago, he stopped taking medication due to an unspecified reason. The patient denied any history of tobacco smoking, alcoholism, and recreational drug use. The patient had a significant family history of hypertension in both his father and mother. Physical examination was unremarkable, and at the time of triage, his blood pressure (BP) was noted as 195/123 mm Hg, equal in both arms. The patient was promptly started on intravenous labetalol with the goal to reduce BP by 15% to 20% in the first hour. The BP was rechecked after an hour of starting labetalol and was 165/100 mm Hg. MRI of the brain was performed in the emergency department and demonstrated multiple scattered areas of increased signal intensity on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images in both the occipital and posterior parietal lobes. There were also similar lesions in both hemispheres of the cerebellum (especially the cerebellar white matter on the left) as well as in the medulla oblongata. The lesions were not associated with mass effect, and after contrast administration, there was no evidence of abnormal enhancement. In the emergency department, his BP decreased to 160/95 mm Hg, and he was transitioned from drip to oral medications and transferred to the telemetry floor. How would you manage this case?

The patient initially presented with headache, nausea, vomiting, blurred vision, and confusion. The patient’s BP was found to be 195/123 mm Hg, and MRI of the brain demonstrated scattered lesions with increased intensity in the occipital and posterior parietal lobes, as well as in cerebellum and medulla oblongata. The clinical presentation, elevated BP, and brain MRI findings were suggestive of hypertensive emergency, more specifically hypertensive encephalopathy. These MRI changes can be seen particularly in posterior reversible encephalopathy syndrome (PRES), a sequela of hypertensive encephalopathy. BP was initially controlled by labetalol, and after satisfactory control of BP, the patient was switched to oral antihypertensive medications.

Hypertensive emergency refers to the elevation of systolic BP >180 mm Hg and/or diastolic BP >120 mm Hg that is associated with end-organ damage; however, in some conditions such as pregnancy, more modest BP elevation can constitute an emergency. An equal degree of hypertension but without end-organ damage constitutes a hypertensive urgency, the treatment of which requires gradual BP reduction over several hours. Patients with hypertensive emergency require rapid, tightly controlled reductions in BP that avoid overcorrection. Management typically occurs in an intensive care setting with continuous arterial BP monitoring and continuous infusion of antihypertensive agents.

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Clinical pearls, case study: treating hypertension in patients with diabetes.

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Evan M. Benjamin; Case Study: Treating Hypertension in Patients With Diabetes. Clin Diabetes 1 July 2004; 22 (3): 137–138. https://doi.org/10.2337/diaclin.22.3.137

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L.N. is a 49-year-old white woman with a history of type 2 diabetes,obesity, hypertension, and migraine headaches. The patient was diagnosed with type 2 diabetes 9 years ago when she presented with mild polyuria and polydipsia. L.N. is 5′4″ and has always been on the large side,with her weight fluctuating between 165 and 185 lb.

Initial treatment for her diabetes consisted of an oral sulfonylurea with the rapid addition of metformin. Her diabetes has been under fair control with a most recent hemoglobin A 1c of 7.4%.

Hypertension was diagnosed 5 years ago when blood pressure (BP) measured in the office was noted to be consistently elevated in the range of 160/90 mmHg on three occasions. L.N. was initially treated with lisinopril, starting at 10 mg daily and increasing to 20 mg daily, yet her BP control has fluctuated.

One year ago, microalbuminuria was detected on an annual urine screen, with 1,943 mg/dl of microalbumin identified on a spot urine sample. L.N. comes into the office today for her usual follow-up visit for diabetes. Physical examination reveals an obese woman with a BP of 154/86 mmHg and a pulse of 78 bpm.

What are the effects of controlling BP in people with diabetes?

What is the target BP for patients with diabetes and hypertension?

Which antihypertensive agents are recommended for patients with diabetes?

Diabetes mellitus is a major risk factor for cardiovascular disease (CVD). Approximately two-thirds of people with diabetes die from complications of CVD. Nearly half of middle-aged people with diabetes have evidence of coronary artery disease (CAD), compared with only one-fourth of people without diabetes in similar populations.

Patients with diabetes are prone to a number of cardiovascular risk factors beyond hyperglycemia. These risk factors, including hypertension,dyslipidemia, and a sedentary lifestyle, are particularly prevalent among patients with diabetes. To reduce the mortality and morbidity from CVD among patients with diabetes, aggressive treatment of glycemic control as well as other cardiovascular risk factors must be initiated.

Studies that have compared antihypertensive treatment in patients with diabetes versus placebo have shown reduced cardiovascular events. The United Kingdom Prospective Diabetes Study (UKPDS), which followed patients with diabetes for an average of 8.5 years, found that patients with tight BP control (< 150/< 85 mmHg) versus less tight control (< 180/< 105 mmHg) had lower rates of myocardial infarction (MI), stroke, and peripheral vascular events. In the UKPDS, each 10-mmHg decrease in mean systolic BP was associated with a 12% reduction in risk for any complication related to diabetes, a 15% reduction for death related to diabetes, and an 11% reduction for MI. Another trial followed patients for 2 years and compared calcium-channel blockers and angiotensin-converting enzyme (ACE) inhibitors,with or without hydrochlorothiazide against placebo and found a significant reduction in acute MI, congestive heart failure, and sudden cardiac death in the intervention group compared to placebo.

The Hypertension Optimal Treatment (HOT) trial has shown that patients assigned to lower BP targets have improved outcomes. In the HOT trial,patients who achieved a diastolic BP of < 80 mmHg benefited the most in terms of reduction of cardiovascular events. Other epidemiological studies have shown that BPs > 120/70 mmHg are associated with increased cardiovascular morbidity and mortality in people with diabetes. The American Diabetes Association has recommended a target BP goal of < 130/80 mmHg. Studies have shown that there is no lower threshold value for BP and that the risk of morbidity and mortality will continue to decrease well into the normal range.

Many classes of drugs have been used in numerous trials to treat patients with hypertension. All classes of drugs have been shown to be superior to placebo in terms of reducing morbidity and mortality. Often, numerous agents(three or more) are needed to achieve specific target levels of BP. Use of almost any drug therapy to reduce hypertension in patients with diabetes has been shown to be effective in decreasing cardiovascular risk. Keeping in mind that numerous agents are often required to achieve the target level of BP control, recommending specific agents becomes a not-so-simple task. The literature continues to evolve, and individual patient conditions and preferences also must come into play.

While lowering BP by any means will help to reduce cardiovascular morbidity, there is evidence that may help guide the selection of an antihypertensive regimen. The UKPDS showed no significant differences in outcomes for treatment for hypertension using an ACE inhibitor or aβ-blocker. In addition, both ACE inhibitors and angiotensin II receptor blockers (ARBs) have been shown to slow the development and progression of diabetic nephropathy. In the Heart Outcomes Prevention Evaluation (HOPE)trial, ACE inhibitors were found to have a favorable effect in reducing cardiovascular morbidity and mortality, whereas recent trials have shown a renal protective benefit from both ACE inhibitors and ARBs. ACE inhibitors andβ-blockers seem to be better than dihydropyridine calcium-channel blockers to reduce MI and heart failure. However, trials using dihydropyridine calcium-channel blockers in combination with ACE inhibitors andβ-blockers do not appear to show any increased morbidity or mortality in CVD, as has been implicated in the past for dihydropyridine calcium-channel blockers alone. Recently, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) in high-risk hypertensive patients,including those with diabetes, demonstrated that chlorthalidone, a thiazide-type diuretic, was superior to an ACE inhibitor, lisinopril, in preventing one or more forms of CVD.

L.N. is a typical patient with obesity, diabetes, and hypertension. Her BP control can be improved. To achieve the target BP goal of < 130/80 mmHg, it may be necessary to maximize the dose of the ACE inhibitor and to add a second and perhaps even a third agent.

Diuretics have been shown to have synergistic effects with ACE inhibitors,and one could be added. Because L.N. has migraine headaches as well as diabetic nephropathy, it may be necessary to individualize her treatment. Adding a β-blocker to the ACE inhibitor will certainly help lower her BP and is associated with good evidence to reduce cardiovascular morbidity. Theβ-blocker may also help to reduce the burden caused by her migraine headaches. Because of the presence of microalbuminuria, the combination of ARBs and ACE inhibitors could also be considered to help reduce BP as well as retard the progression of diabetic nephropathy. Overall, more aggressive treatment to control L.N.'s hypertension will be necessary. Information obtained from recent trials and emerging new pharmacological agents now make it easier to achieve BP control targets.

Hypertension is a risk factor for cardiovascular complications of diabetes.

Clinical trials demonstrate that drug therapy versus placebo will reduce cardiovascular events when treating patients with hypertension and diabetes.

A target BP goal of < 130/80 mmHg is recommended.

Pharmacological therapy needs to be individualized to fit patients'needs.

ACE inhibitors, ARBs, diuretics, and β-blockers have all been documented to be effective pharmacological treatment.

Combinations of drugs are often necessary to achieve target levels of BP control.

ACE inhibitors and ARBs are agents best suited to retard progression of nephropathy.

Evan M. Benjamin, MD, FACP, is an assistant professor of medicine and Vice President of Healthcare Quality at Baystate Medical Center in Springfield, Mass.

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Hypertension and 24-hour ambulatory blood pressure monitoring.

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Patient Case Presentation

Mr. E.A. is a 40-year-old black male who presented to his Primary Care Provider for a diabetes follow up on October 14th, 2019. The patient complains of a general constant headache that has lasted the past week, with no relieving factors. He also reports an unusual increase in fatigue and general muscle ache without any change in his daily routine. Patient also reports occasional numbness and tingling of face and arms. He is concerned that these symptoms could potentially be a result of his new diabetes medication that he began roughly a week ago. Patient states that he has not had any caffeine or smoked tobacco in the last thirty minutes. During assessment vital signs read BP 165/87, Temp 97.5 , RR 16, O 98%, and HR 86. E.A states he has not lost or gained any weight. After 10 mins, the vital signs were retaken BP 170/90, Temp 97.8, RR 15, O 99% and HR 82. Hg A1c 7.8%, three months prior Hg A1c was 8.0%.  Glucose  180 mg/dL (fasting).  FAST test done; negative for stroke. CT test, Chem 7 and CBC have been ordered.

Past medical history

Diagnosed with diabetes (type 2) at 32 years old

Overweight, BMI of 31

Had a cholecystomy at 38 years old

Diagnosed with dyslipidemia at 32 years old

Past family history

Mother alive, diagnosed diabetic at 42 years old 

Father alive with Hypertension diagnosed at 55 years old

Brother alive and well at 45 years old

Sister alive and obese at 34 years old 

Pertinent social history

Social drinker on occasion

Smokes a pack of cigarettes per day

Works full time as an IT technician and is in graduate school

• Introduction
• Conclusions
• Article Information

AD indicates atopic dermatitis; OCS, oral corticosteroid.

a Rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, psoriasis, Crohn disease, ulcerative colitis, Sjögren syndrome, systemic sclerosis, dermatomyositis, polymyositis, thromboangiitis obliterans, Behçet disease, sarcoidosis, pemphigus, and vitiligo.

b Patients who received a diagnosis of the outcomes of interest (osteoporosis, fracture, type 2 diabetes, hyperlipidemia, hypertension, myocardial infarction, stroke, heart failure, avascular necrosis, cataract, or glaucoma) during 1 year before or 1 year after the cohort entry date were excluded.

OR indicates odds ratio.

a Modified definition of the exposure from cumulative duration of more than 30 days per year and more than 90 days per year to a cumulative duration of more than 60 days per year.

b The long-term use of oral corticosteroids was defined as a cumulative supply of more than 30 days or more than 90 days with a greater than 5-mg daily prednisolone-equivalent dose of oral corticosteroids, which places patients at risk of systemic adverse effects, and we assessed the long-term use of oral corticosteroids annually. To exclude potential use of oral corticosteroids for conditions other than atopic dermatitis, we restricted exposure to prescriptions for patients with a diagnosis of atopic dermatitis.

c Restricted to patients who could be followed up for at least 3 years from the cohort entry date.

d Restricted to patients who could be followed up for at least 5 years from the cohort entry date.

eTable 1. Demographic and Clinical Characteristics of Cases and Controls of Adult Patients (>18 Years) With Atopic Dermatitis for Composite Outcome

eTable 2. Codes Used to Define Exclusion Criteria, Exposures, Outcomes, and Covariates

eTable 3. Exposure Definition Regarding to Long-Term Oral Corticosteroid Usage in the Previous Studies

eTable 4. Demographic and Clinical Characteristics of Cases and Controls of Adult Patients (>18 Years) With Atopic Dermatitis, Comparison Between Ever Long-Term Use of OCS Over 30 Days vs 90 Days

eTable 5. Demographic and Clinical Characteristics of Cases and Controls of Adult Patients (>18 Years) With Atopic Dermatitis: Osteoporosis

eTable 6. Demographic and Clinical Characteristics of Cases and Controls of Adult Patients (>18 Years) With Atopic Dermatitis: Fracture

eTable 7. Demographic and Clinical Characteristics of Cases and Controls of Adult Patients (>18 Years) With Atopic Dermatitis: Type 2 Diabetes Mellitus

eTable 8. Demographic and Clinical Characteristics of Cases and Controls of Adult Patients (>18 Years) With Atopic Dermatitis: Hyperlipidemia

eTable 9. Demographic and Clinical Characteristics of Cases and Controls of Adult Patients (>18 Years) With Atopic Dermatitis: Hypertension

eTable 10. Demographic and Clinical Characteristics of Cases and Controls of Adult Patients (>18 Years) With Atopic Dermatitis: Myocardial Infarction

eTable 11. Demographic and Clinical Characteristics of Cases and Controls of Adult Patients (>18 Years) With Atopic Dermatitis: Stroke

eTable 12. Demographic and Clinical Characteristics of Cases and Controls of Adult Patients (>18 Years) With Atopic Dermatitis: Heart Failure

eTable 13. Demographic and Clinical Characteristics of Cases and Controls of Adult Patients (>18 Years) With Atopic Dermatitis: Avascular Necrosis

eTable 14. Demographic and Clinical Characteristics of Cases and Controls of Adult Patients (>18 Years) With Atopic Dermatitis: Cataract

eTable 15. Demographic and Clinical Characteristics of Cases and Controls of Adult Patients (>18 Years) With Atopic Dermatitis: Glaucoma

eTable 16. E-Values for Point Estimates of Different Outcomes of Interest for Primary Exposure: >30 Days a Year

eTable 17. E-Values for Point Estimates of Different Outcomes of Interest for Primary Exposure: >90 Days a Year

eFigure 1. Overall Design of This Nested-Case Control Study

eFigure 2. Case-Control Matching Using Risk-Set Sampling Method

eFigure 3 . Explanation for the Exposure Status According to 1) Ever Long-Term OCS, 2) Cumulative No. of Years of Long-Term OCS, 3) Consecutive No. of Years of Long-Term OCS for the Primary (>30 Days) and Secondary (>90 Days) Exposure Definition

eFigure 4. Subgroup Analysis According to the Age Stratification for Evaluating the Risk of Composite Adverse Outcomes Associated With Long-Term Use of OCS

eFigure 5. Subgroup Analysis According to the Sex Stratification for Evaluating the Risk of Composite Adverse Outcomes Associated With Long-Term Use of OCS

eFigure 6. Subgroup Analysis According to the Severity of AD Stratification for Evaluating the Risk of Composite Adverse Outcomes Associated With Long-Term Use of OCS

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Jang YH , Choi E , Lee H, et al. Long-Term Use of Oral Corticosteroids and Safety Outcomes for Patients With Atopic Dermatitis. JAMA Netw Open. 2024;7(7):e2423563. doi:10.1001/jamanetworkopen.2024.23563

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Long-Term Use of Oral Corticosteroids and Safety Outcomes for Patients With Atopic Dermatitis

• 1 Department of Dermatology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Korea
• 2 School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
• 3 Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea
• 4 Research Department of Practice and Policy, School of Pharmacy, University College London, London, United Kingdom
• 5 School of Pharmacy, Aston University, Birmingham, United Kingdom
• 6 Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada
• 7 Department of Inflammation & Immunology Medical Affairs, Pfizer Pharmaceuticals Korea Ltd, Seoul, South Korea
• 8 Department of Clinical Research Design & Evaluation, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, South Korea
• 9 Department of Dermatology, Konkuk University School of Medicine, Seoul, South Korea

Question   What duration of oral corticosteroid use is associated with adverse effects among adult patients with atopic dermatitis?

Findings   In this nested case-control study including 1 025 270 patients with atopic dermatitis, use of oral corticosteroids for more than 90 days during 1 year was associated with a slightly increased risk of composite adverse outcomes. There was no increased risk with use of oral corticosteroids for more than 30 days.

Meaning   This study suggests that for patients with exacerbations of atopic dermatitis, limiting the duration of oral corticosteroid treatment to 90 days or less may limit adverse effects.

Importance   The use of oral corticosteroids for prolonged periods may be associated with adverse events (AEs). Nevertheless, the risk of AEs with oral corticosteroids, especially among patients with atopic dermatitis (AD), has not been comprehensively investigated and lacks evidence on duration of treatment.

Objective   To assess the association between long-term exposure to oral corticosteroids and AEs among adult patients with AD.

Design, Setting, and Participants   This nested case-control study used data from the Health Insurance Review and Assessment Service database of South Korea between January 1, 2012, and October 31, 2021, which included 1 year prior to the cohort entry date of January 1, 2013, for assessing exclusion criteria and baseline characteristics, and 1 year after the study end date of October 31, 2020, to ensure a minimum duration for assessing exposure. Among the population of adults with AD, patients diagnosed with any of 11 AEs were matched with patients who had never received a diagnosis of any of the 11 AEs.

Exposure   Long-term use of oral corticosteroids was defined as cumulative supply of more than 30 days or more than 90 days of oral corticosteroid prescription per year.

Main Outcomes and Measures   We used multivariable conditional logistic regression analyses to measure the risk of 11 individual outcomes (osteoporosis, fracture, type 2 diabetes, hyperlipidemia, hypertension, myocardial infarction, stroke, heart failure, avascular necrosis, cataract, or glaucoma) as the composite outcome, controlling for potential confounders. We further classified the composite outcome to individual outcomes to evaluate the AE-specific risk.

Results   Among 1 025 270 patients with AD between 2013 and 2020, 164 809 cases (mean [SD] age, 39.4 [14.8]; 56.9% women) were matched with 328 303 controls (mean [SD] age, 39.3 [14.7]; 56.9% women) for sex, age, cohort entry date, follow-up duration, and severity of AD, where the balance of most baseline characteristics was achieved. A total of 5533 cases (3.4%) and 10 561 controls (3.2%) were exposed to oral corticosteroids for more than 30 days, while 684 cases (0.4%) and 1153 controls (0.4%) were exposed to oral corticosteroids for more than 90 days. Overall, there was no increased risk of AEs with use of oral corticosteroids for more than 30 days (adjusted odds ratio [AOR], 1.00; 95% CI, 0.97-1.04), whereas the risk was slightly higher with use of oral corticosteroids for more than 90 days (AOR, 1.11; 95% CI, 1.01-1.23). The small elevation in experiencing an AE was observed with each cumulative or consecutive year of ever long-term use.

Conclusions and Relevance   This case-control study found a slightly increased risk of AEs associated with use of oral corticosteroids for more than 90 days per year, which warrants future research to fully elucidate the observed findings.

Atopic dermatitis (AD) is a chronic inflammatory disease that causes serious morbidity, such as pruritus, impaired quality of life, and a range of comorbidities. 1 , 2 AD is a lifelong condition that relapses chronically and needs constant care. 3 Although AD is considered primarily a pediatric disease, studies have shown high rates of AD among adults as well. 4 The prevalence of AD among adults ranged from 2.1% to 4.9% across countries, and up to 10% of adults required medication for moderate to severe AD due to inadequate response to topical therapies; the prevalence rates were higher among adult patients than among pediatric patients, of whom 1.5% required medication for moderate to severe AD. 5 - 7

As AD treatment strategies, international guidelines and expert opinions generally recommend that oral corticosteroids should generally be avoided or limited to the short term only as rescue therapy. 8 - 11 Nonetheless, given the benefits of oral corticosteroids, including their effectiveness in allergic diseases, short-term safety, and low cost, many patients with moderate to severe AD are treated with oral corticosteroids for prolonged periods, which may constitute inappropriate or excessive use. 12 , 13 However, oral corticosteroid treatment for prolonged periods could have an association with oral corticosteroid–related complications. 14 Hence, clinical evidence informing patients and practitioners regarding the management of AD exacerbations in routine clinical practice is warranted.

Although previous studies among patients with asthma or rheumatic disease have suggested associations between long-term use of oral corticosteroids and various adverse events (AEs), there are few studies of patients with AD, to our knowledge. 15 - 21 In addition, existing studies about corticosteroid use among patients with AD were conducted to evaluate the safety concerns primarily about topical corticosteroids. 22 - 29 Considering the frequent use of oral corticosteroids among adults with AD and the potential association between long-term use of oral corticosteroids and AEs, some of which are severe, there is a need to investigate the safety of the long-term use of oral corticosteroids among adults with AD. 6 , 30 , 31 Accordingly, we aimed to investigate the association between long-term use of oral corticosteroids and AEs among adult patients with AD in South Korea.

We used the nationwide Health Insurance Review and Assessment Service (HIRA) database of South Korea between January 1, 2012, and October 31, 2021, which included 1 year prior to the cohort entry date of January 1, 2013, for assessing exclusion criteria and baseline characteristics, and 1 year after the study end date of October 31, 2020, to ensure a minimum duration for assessing exposure. It encompasses comprehensive data on health care use for every resident of South Korea, ensuring that patient identifiers are anonymized. The database collects information on socioeconomic and demographic variables, diagnosis ( International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic code; setting of diagnosis; date of diagnosis; and others), and medications prescribed (national drug chemical code, days’ supply, dose, date of prescription, route of administration, and others) until the occurrence of emigration or death. A prior validation study examined diagnosis codes documented in the HIRA in comparison with those in electronic medical records and found an overall positive predictive value of 82.3%. 32 This study was approved by the institutional review board of Sungkyunkwan University, which waived the informed consent because only deidentified data were used in this study. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) reporting guideline. 33

The study cohort comprised patients who were prescribed oral corticosteroids at least once with an AD diagnosis code from January 1, 2013, to October 31, 2020. The cohort entry date was defined as the first date of the prescription of oral corticosteroids with an AD diagnosis within the study period to include the new users of oral corticosteroids. Eligible case and control groups were identified after excluding the following: (1) patients with a diagnosis of immune-mediated inflammatory diseases during a 1-year window of exclusion assessment before the cohort entry date, to evaluate the risk of AEs from oral corticosteroid use for AD; (2) patients with a diagnosis of any of 11 outcomes of interest during the exclusion assessment window of 1 year before and 1 year after the cohort entry date, to investigate the association of oral corticosteroid use with newly occurred outcomes; and (3) patients who were younger than 18 years of age on the cohort entry date, to include adult patients ( Figure 1 ).

Cases were defined as patients with AD who received a diagnosis of any of our outcomes of interest after the cohort entry date, and the index date was defined as the first date of outcome occurrence. The composite outcome of interest consisted of osteoporosis, fracture, type 2 diabetes, hyperlipidemia, hypertension, myocardial infarction, stroke, heart failure, avascular necrosis (AVN), cataract, and glaucoma. We defined controls as patients with AD who never received a diagnosis of our outcomes of interests after the cohort entry date. We matched each case with up to 2 controls without replacement, using risk-set sampling on the cohort entry date (±30 days), follow-up duration (between the cohort entry date and the index date [±30 days]), age, sex, and severity of AD. Disease severity of AD was classified as moderate to severe on the basis of the current treatment guidelines for AD. 7 Moderate to severe AD was defined as patients who were receiving at least 1 immunosuppressant, alitretinoin, intravenous immunoglobulin, dupilumab, or phototherapy during the 1 year prior to the cohort entry date. The index dates of the control group were aligned with the corresponding index date of their respective matched cases. For individual outcomes, each case was matched with up to 5 or 10 controls, using different numbers from the composite outcome for ensuring statistical power according to the size of cases for each outcome variable, using risk-set sampling as well (eFigure 2 in Supplement 1 ).

We defined the exposure ascertainment window as the period between the cohort entry date and the index date, segmenting the period into yearly intervals to assess exposure year by year to determine whether patients met the definition for long-term use of oral corticosteroids. Owing to the absence of consensus for a definition of long-term oral corticosteroid use among patients with AD, and even for other diseases, we set the classification of long-term oral corticosteroid use as follows: cumulatively more than 30 days as the primary definition for modest long-term use or more than 90 days as a secondary definition for extensive long-term use, both with greater than a 5-mg daily prednisolone-equivalent dose of oral corticosteroids per year, which places patients at risk of systemic adverse effects. 17 To exclude potential use of oral corticosteroids for related conditions other than AD, we restricted exposure to prescriptions of oral corticosteroids to patients with a diagnosis of AD. Ever long-term use was defined as patients with a history of long-term use of oral corticosteroids for at least 1 year, and all remaining patients were defined as no long-term use . Primarily, ever long-term use was defined as a binary variable using 2 thresholds (>30 days and >90 days). In addition, to examine the duration-response association with long-term use of oral corticosteroids, we used the year, which met the definition for the long-term use, as a continuous variable. We assessed the risk of each outcome associated with the number of cumulative years (considering all the intermittent years of long-term use of oral corticosteroids) throughout the exposure ascertainment period. We also evaluated the risk associated with the number of consecutive years (considering only the continuous years of long-term use of oral corticosteroids) within the exposure ascertainment period. Details of the exposure assessment are shown in eFigure 3 in Supplement 1 .

We discerned a sufficient collection of confounding variables that adequately accounted for potential biases in our analysis: demographic characteristics (eg, sex, age, and medical aid recipients), comorbidities (eg, allergic rhinitis, depression, chronic obstructive pulmonary disease, and thyroid disorders), comedications (eg, antidepressants, antibiotics, estrogens, and proton-pump inhibitors), proxies of overall health status (eg, history of hospitalization, number of outpatient visits, and Charlson Comorbidity Index score), and severity of AD. The characteristic assessment window was defined as the 1-year period before the cohort entry date (eFigure 1 in Supplement 1 ; the demographic characteristics [sex, age, insurance] were assessed on the cohort entry date and other characteristics such as comorbidities, comedications, proxies of health status, and severity of AD during the 1 year prior to cohort entry). The details of exclusion criteria, exposures, outcomes, and covariates are presented in eTable 2 in Supplement 1 .

The demographic characteristics of the cases and controls were presented as frequency (proportion) for categorical variables and as mean (SD) or median (IQR) values for continuous variables. The same analysis used to evaluate the demographic characteristics of the cases and controls of patients with AD were repeated for each of the 11 outcomes as secondary outcomes. Differences in baseline covariates between cases and controls were evaluated using the absolute standardized difference, where an absolute standardized difference greater than 0.1 indicates a statistical imbalance existing between 2 groups.

The association between long-term oral corticosteroid use and the risk of the composite and individual outcomes were investigated using multivariable conditional logistic regression analyses to estimate adjusted odds ratios (AORs) with 95% CIs, adjusting for unbalanced comorbidities, comedications, and proxies of health status after the matching. We conducted additional analyses by considering the number of cumulative or consecutive years of long-term use of oral corticosteroids throughout the entire exposure ascertainment window as continuous variables, to investigate the monotonic duration-response association.

The potential heterogeneity of long-term treatment adverse effects in selected subgroups of patients with AD was examined for the composite adverse outcomes according to age (18-39, 40-64, and ≥65 years), sex (male or female), and severity of AD (mild or moderate to severe AD). To evaluate the robustness of the main findings, sensitivity analyses were first conducted by modifying the definition of exposure from a cumulative duration of more than 30 days or more than 90 days per year to more than 60 days per year. Second, we restricted the population to patients who could be followed up for at least 3 years or 5 years from the cohort entry date. All statistical tests were 2 sided. Analyses were conducted using SAS Enterprise Guide, version 7.1 (SAS Institute Inc), provided by HIRA through a virtual access machine.

Of 1 025 270 patients with AD who had at least 1 prescription of oral corticosteroids between 2013 and 2020, we matched 164 809 cases (mean [SD] age, 39.4 [14.8]; 56.9% women and 43.1% men) with 328 303 controls (mean [SD] age, 39.3 [14.7]; 56.9% women and 43.1% men) ( Table 1 ) by 1:2 matching using risk-set sampling. Cases and controls were matched for sex, age, cohort entry date, follow-up duration, and severity of AD; balance was achieved for most covariates between the 2 groups, with an absolute standardized difference of less than 0.1 ( Table 1 ; whole baseline characteristics of cases and controls are presented in eTable 1 in Supplement 1 , individual outcomes in eTables 5-15 in Supplement 1 , and modest long-term [>30 days] vs extensive long-term [>90 days] in eTable 4 in Supplement 1 ). The most common comorbidity was allergic rhinitis (cases, 42.2%; controls, 38.7%), and the most prevalently prescribed concurrent medication was antibiotics (cases, 71.3% and controls, 66.8%). All the imbalanced variables of concurrent medication use and number of outpatient visits were additionally adjusted in the multivariable logistic regression.

Among the 164 809 cases and 328 303 controls, 5533 cases (3.4%) and 10 561 controls (3.2%) were exposed to oral corticosteroids over 30 days, and 684 cases (0.4%) and 1153 controls (0.4%) were exposed to oral corticosteroids over 90 days. Overall, the risk of AEs was not associated with use of oral corticosteroids exceeding 30 days (AOR, 1.00; 95% CI, 0.97-1.04) ( Table 2 ), while use of oral corticosteroids exceeding 90 days was associated with an 11% increased risk of the composite adverse outcome (AOR, 1.11; 95% CI, 1.01-1.23) ( Table 3 ). Each cumulative or consecutive additive year of long-term exposure (>90 days a year) was associated with a slightly increased risk of having an AE (AOR, 1.06; 95% CI, 1.00-1.13 and AOR, 1.06; 95% CI, 1.00-1.13, respectively).

In the analyses of individual outcomes, an increased risk for hypertension (AOR, 1.09; 95% CI, 1.03-1.15), AVN (AOR, 2.56; 95% CI, 1.82-3.62), and cataract (AOR, 3.22; 95% CI, 1.05-9.85) was associated with use of oral corticosteroids for more than 30 days ( Table 2 ). An increased risk for fracture (AOR, 1.22; 95% CI, 1.05-1.42), hyperlipidemia (AOR, 1.16; 95% CI, 1.03-1.30), myocardial infarction (AOR, 2.22; 95% CI, 1.17-4.22), and AVN (AOR, 6.88; 95% CI, 3.53-13.42) was associated with use of oral corticosteroids for more than 90 days ( Table 3 ). In our subgroup analysis, as compared with unexposed patients, the risk of composite AEs associated with long-term use of oral corticosteroids was generally consistent with the main analyses. No differences were observed in the stratified analyses according to the age group, sex, and severity of AD (eFigures 4-6 in Supplement 1 ). Furthermore, the results of composite outcomes demonstrated a high degree of consistency across all sensitivity analyses regarding the point estimates ( Figure 2 ).

We identified 164 809 cases and 328 303 controls of comparable patients with AD. The risk of composite adverse outcomes was not associated with with ever long-term use of oral corticosteroids exceeding 30 days, whereas the risk was slightly associated with ever long-term use exceeding 90 days. Also, the cumulative and consecutive years of ever long-term use throughout entire exposure ascertainment period was associated with a monotonic elevated risk of having an AE, although there was not a large discrepancy between the 2 distinctive analyses of additive years. Furthermore, small increased risks were identified in the examination of individual outcomes of fracture, hyperlipidemia, hypertension, myocardial infarction, AVN, and cataract. Generally consistent findings, with regard to point estimates, were observed across a range of sensitivity analyses.

Considering the overlapping pathogenetic mechanism between AD and asthma, we referred to studies of patients with asthma for comparison. One cohort study using Medicaid data found that the use of medium and high doses of systemic corticosteroids was associated with bone, cardiovascular, metabolic, and ocular AEs. 34 Another cohort study using 2000-2014 MarketScan data showed a similar increased risk of various AEs associated with the use of 1 to 3 oral corticosteroid prescriptions (AOR, 1.04; 95% CI, 1.01-1.06) and the use of 4 or more prescriptions (AOR, 1.29; 95% CI, 1.20-1.37); the cumulative burden also increased as the number of years accumulated. 20 Although previous research evaluated the frequency of oral corticosteroid use based on prescription numbers, our study provided more conclusive and valid clinical evidence by defining long-term use based on exact duration.

For individual outcomes, in line with previous studies, we also identified fracture, hypertension, hyperlipidemia, and myocardial infarction as AEs associated with long-term use of oral corticosteroids, owing to interruption of endocrine function and metabolism. 20 , 35 - 38 We observed risks of AVN and cataract with long-term oral corticosteroid use, although the risks of these 2 conditions were inconclusive in past studies. For the underlying mechanisms for AVN of the femoral head, the use of oral corticosteroids leads to intravascular coagulation that results in a inhibition of blood flow to the bones, which consequently triggers ischemic injury. 39 - 41 Although existing evidence regarding an association of AVN with duration of oral corticosteroid treatment is unclear, AVN could be induced from use of just over 30 days, and cumulative exposure is the important determining factor, as shown in our results. 39 Furthermore, although a complete elucidation remains uncertain, the mechanisms of new-onset cataract associated with modest long-term use of oral corticosteroids may be due to disturbances in osmotic equilibrium, oxidative detriment, and perturbations in lens growth factors. 42 , 43 Another potential hypothesis involves nonenzymatic Schiff base intermediates that form between the corticosteroid’s C-20 ketone group and its nucleophilic groups, undergoing Heyns rearrangement to produce stable amine-substituted adducts seen only in corticosteroid-induced posterior subcapsular cataracts. 44 , 45 No association or subtle increased hazard was observed with osteoporosis, glaucoma, stroke, or heart failure, implying that the dose and duration of corticosteroid treatment may not pose a risk for these conditions among patients with AD.

This study has some strengths. Concerns about conducting this study arose from the lack of consensus regarding the definition of long-term corticosteroid treatment, as different criteria have been used and variations have been observed (eTable 3 in Supplement 1 ). Accordingly, we combined the NICE (National Institute for Health and Care Excellence) guidelines 17 with the opinions of clinicians practicing in clinical settings. Even though evidence for a safe continuous duration of corticosteroid treatment was not available as we developed criteria for the definition of long-term treatment for the dichotomous variable, our criteria are expected to serve as a primary threshold for deciding the duration of treatment. In addition, although the long-term use of oral corticosteroids is not recommended in the guideline for treatment of AD, relatively prolonged use of oral corticosteroids is identified frequently in clinical practice. 12 Thus, this study addresses a significant gap in research by investigating the association between long-term oral corticosteroid use and a comprehensive range of AEs specifically among adults with AD. With its substantial sample size, the study provides robust statistical power to detect associations between oral corticosteroid use and relatively rare outcomes, adding to the existing evidence.

This study also has some limitations. First, disparities arose between the diagnoses recorded and the actual diseases a patient had. 46 In addition, HIRA data do not include clinical data; accordingly, the diagnostic standard criteria for AD, such as the Hanifin-Rajka criteria, 47 , 48 were infeasible. To comply with this issue, we included patients with AD who had at least 1 oral corticosteroid prescription and restricted prescriptions to patients with a diagnosis of AD. Second, due to the inbuilt characteristics of database recording drugs that are prescribed rather than drugs that are taken, the exposure measurement could be uncertain. However, we set the exposed group from the modest long term (>30 days) to the extensive long term (>90 days) and also included the numbers of cumulative or consecutive years of ever long-term use, from which the cumulative burden would be appropriately measured. Third, inhaled corticosteroids, which have some degree of systemic bioavailability, and topical and eye drop formulations of corticosteroids were not accounted for in this study. Fourth, for some of the individual study outcomes, we could not rule out the failure to detect the true effect due to the lack of statistical power; thus, future studies are warranted to corroborate these results. Fifth, due to the nature of the case-control design, it is not possible to completely exclude reverse causality. Sixth, although we considered moderate to severe AD using prescriptions of medication based on the treatment guideline, the influence of AD-related disease severity cannot be eliminated. Seventh, we addressed residual or unmeasured confounders by calculating E-values (eTables 16 and 17 in Supplement 1 ), but unmeasured confounders may be present, and the results should be interpreted with caution.

In this large population-based case-control study, we discovered that oral corticosteroid use of more than 90 days among individuals with AD was associated with a small increased risk of composite adverse outcomes. Future investigations are warranted to confirm this potential risk of AEs associated with long-term use of oral corticosteroids for patients with exacerbations of AD, and health care professionals should thoroughly weigh the benefits associated with oral corticosteroids against the observed small risk of AEs, while continuously monitoring for AEs.

Accepted for Publication: May 23, 2024.

Published: July 19, 2024. doi:10.1001/jamanetworkopen.2024.23563

Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License . © 2024 Jang YH et al. JAMA Network Open .

Corresponding Authors: Ju-Young Shin, PhD, School of Pharmacy, Sungkyunkwan University, 2066 Saburo, Jangan-gu, Suwon, Gyeonggi-do 16419, South Korea ( [email protected] ); Yang Won Lee, MD, PhD, Department of Dermatology, Konkuk University School of Medicine, 120-1 Neungdong-ro, Gwangjin-gu, Seoul 05030, South Korea ( [email protected] ).

Author Contributions: Drs Shin and Y. W. Lee had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Jang and Choi contributed equally to this work.

Concept and design: All authors.

Acquisition, analysis, or interpretation of data: H. Lee, Noh, Jeon, Yoo.

Drafting of the manuscript: Jang, Choi, Woo, Jeon, Yoo.

Critical review of the manuscript for important intellectual content: Jang, H. Lee, Woo, Park, Noh, Jeon, Yoo, Shin, Y. W. Lee.

Statistical analysis: Choi, H. Lee, Woo, Park.

Obtained funding: Jeon, Yoo, Shin.

Administrative, technical, or material support: Jeon, Yoo, Shin, Y. W. Lee.

Supervision: Jang, Shin.

Conflict of Interest Disclosures: Dr Park reported receiving support from the AIR@innoHK programme of the Government of Hong Kong Special Administrative Region Innovation and Technology Commission. Dr Noh reported receiving grants from the Ministry of Health and Welfare outside the submitted work. Drs Jeon and Yoo reported receiving personal fees from Pfizer Pharmaceuticals Korea Ltd outside the submitted work. Dr Shin reported receiving grants from the Ministry of Food and Drug Safety, the Ministry of Health and Welfare, the National Research Foundation of Korea, Celltrion, and SK Bioscience outside the submitted work. No other disclosures were reported.

Funding/Support: This work was supported by Pfizer Pharmaceuticals Korea Ltd.

Role of the Funder/Sponsor: Pfizer Pharmaceuticals Korea Ltd had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 2 .

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Hypertension: A Case Study

• January 2022
• 8(7):379 - 381

• Adesh Medical College and Hospital

• Eternal University

• Akal College of Nursing Eternal University Baru Sahib.

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Associations of hypertension and antenatal care-seeking with perinatal mortality: A nested case-control study in rural Bangladesh

• Bear, Allyson P.
• Bennett, Wendy L.
• Katz, Joanne
• Lee, Kyu Han
• Chowdhury, Atique Iqbal
• Bari, Sanwarul
• El Arifeen, Shams
• Gurley, Emily S.

Maternal hypertension may be an underrecognized but important risk factor for perinatal death in low resource settings. We investigated the association of maternal hypertension and perinatal mortality in rural Bangladesh. This nested, matched case-control study used data from a 2019 cross-sectional survey and demographic surveillance database in Baliakandi, Bangladesh. We randomly matched each pregnancy ending in perinatal death with five pregnancies in which the neonate survived beyond seven days based on maternal age, education, and wealth quintile. We estimated associations of antenatal care-seeking and self-reported hypertension with perinatal mortality using conditional logistic regression and used median and interquartile ranges to assess the mediation of antenatal care by timing or frequency. Among 191 cases and 934 matched controls, hypertension prevalence was 14.1% among cases and 7.7% among controls. Compared with no diagnosis, the probability of perinatal death was significantly higher among women with a pre-gestational hypertension diagnosis (OR 2.90, 95% CI 1.29, 6.57), but not among women with diagnosis during pregnancy (OR 1.68, 95% CI 0.98, 2.98). We found no association between the number of antenatal care contacts and perinatal death (p = 0.66). Among women with pre-gestational hypertension who experienced a perinatal death, 78% had their first antenatal contact in the sixth or seventh month of gestation. Hypertension was more common among rural women who experience a perinatal death. Greater effort to prevent hypertension prior to conception and provide early maternity care to women with hypertension could improve perinatal outcomes in rural Bangladesh.

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Effectiveness and cost-effectiveness of team-based care for hypertension: a meta-analysis and simulation study

Kelsey b. bryant.

(1) Icahn School of Medicine, Mount Sinai, New York, NY.

Aditi S. Rao

(2) Vagelos College of Physician and Surgeons, Columbia University, New York, NY.

Laura P. Cohen

Nadine dandan.

(3) New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY.

Ian M. Kronish

Nikita barai, valy fontil.

(4) Grossman School of Medicine, New York University, New York, NY.

Andrew E. Moran

Brandon k. bellows, associated data, background:.

Team-based care (TBC), a team of two or more healthcare professionals working collaboratively toward a shared clinical goal, is a recommended strategy to manage blood pressure (BP). However, the most effective and cost-effective TBC strategy is unknown.

A meta-analysis of clinical trials in US adults (aged ≥20 years) with uncontrolled hypertension (≥140/90 mmHg) was performed to estimate the systolic BP (SBP) reduction for TBC strategies vs. usual care at 12 months. TBC strategies were stratified by the inclusion of a non-physician team member who could titrate antihypertensive medications. The validated BP Control Model-Cardiovascular Disease (CVD) Policy Model was used to project the expected BP reductions out to 10 years, and simulate CVD events, direct healthcare costs, quality-adjusted life years (QALYs), and cost-effectiveness of TBC with physician and non-physician titration.

Among 19 studies comprising 5,993 participants, the 12-month SBP change vs. usual care was −5.0 (95% confidence interval: −7.9 to −2.2) mmHg for TBC with physician titration and −10.5 (−16.2 to −4.8) mmHg for TBC with non-physician titration. Relative to usual care at 10 years, TBC with non-physician titration was estimated to cost $95 (95% uncertainty interval: -$563 to $664) more per patient and gain 0.022 (0.003 to 0.042) QALYs, costing $4,400/QALY gained. TBC with physician titration was estimated to cost more and gain fewer QALYs than TBC with non-physician titration.

Conclusions:

TBC with non-physician titration yields superior hypertension outcomes compared with other strategies and is a cost-effective way to reduce hypertension-related morbidity and mortality in the US.

INTRODUCTION

Blood pressure (BP) control rates worsened by 10% from 2013-2014 to 2017-2018 despite the availability of effective antihypertensive medications. 1 In order to improve BP control and reduce associated cardiovascular disease (CVD) morbidity and mortality, it is important to understand the most efficient and effective care delivery strategies to guide program design and health policy development. 1

Team-based care (TBC), i.e., healthcare services delivered by two or more providers working collaboratively, is a hypertension control strategy recommended by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) BP guideline and the 2020 US Surgeon General’s Call to Action to Control Hypertension. 2 - 4 TBC has been associated with improved rates of BP control compared with usual primary care. 5 , 6 Additionally, TBC with non-physician team members who can manage medications (e.g., pharmacists, nurse practitioners), is associated with greater BP reductions compared with programs where only physicians can manage medications. 6 However, training and deploying non-physician team members to manage antihypertensive medications may be costly to clinics and healthcare systems.

Reversing recent BP control trends and meeting quality benchmarks may require healthcare organizations to substantially change usual hypertension care processes. 7 However, the most clinically effective and cost-effective TBC design, including TBC impact on hypertension care processes (e.g., provider visit frequency, clinical inertia, and optimal length of the program) is unknown. We therefore performed a meta-analysis and simulation to estimate the effectiveness and cost-effectiveness of TBC program strategies for hypertension management.

The data that support the findings of the meta-analysis are available from Dr. Bellows upon reasonable request. The simulation model and key inputs used for the cost-effectiveness analysis are available on reasonable request and approval by the research team. Interested researchers will be asked to submit a 1- to 2-page research proposal and collaboration plan to Dr. Bellows and will be required to sign a Creative Commons agreement.

Meta-Analysis

Data searches and study inclusion.

Randomized controlled trials were identified through a literature search performed using PubMed and from prior systematic reviews and meta-analyses ( Supplemental Methods ). 5 , 6 , 8 Studies were included if they were (1) performed in the US, (2) published after 1/1/2003, (3) had a duration of ≥6 months, (4) included a TBC arm, and (5) included participants with uncontrolled BP at baseline, defined as systolic BP (SBP) ≥140 mmHg or ≥130 mmHg in those with diabetes or chronic kidney disease. Studies were excluded if they did not report sufficient data on BP outcomes, did not report outcomes at six months, or did not report information such as standard deviations or confidence intervals for BP outcomes.

Data Extraction

Data extraction was performed using a standardized tool in the Covidence systematic review software (Veritas Health Innovation, Melbourne, Australia). Data were extracted by authors KBB, ASR, LPC, and BKB, with all data extracted verified by a second team member. All data extracted are described in the Supplemental Methods .

The primary outcomes were SBP change at six and twelve months for TBC vs. usual care ( Supplemental Methods ). Secondary outcomes included diastolic BP (DBP) change and BP control at six and twelve months. All outcomes assessed compared with usual care, which was generally defined across studies as hypertension management by a primary care physician without non-physician team member support.

Quality Assessment

We used the Cochrane Risk of Bias 2 tool for randomized controlled trials to assess the quality of the data collected. 9 Each paper was assessed by two independent reviewers (KBB, ASR, LPC, and BKB), with differences resolved by consensus with a third reviewer.

Statistical Analyses

The meta-analysis adhered to practices recommended in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses ( Table S1 ). The meta-analysis was performed using Stata version 16.1 (StataCorp LLC, College Station, TX) using random effects models to generate weighted mean differences of SBP and DBP outcomes and percent difference in BP control. Analyses were stratified by whether a physician or non-physician team (e.g., pharmacist, nurse practitioner) member performed antihypertensive medication titration. When there were two or more intervention arms meeting inclusion criteria within a given study, they were each included in the meta-analysis, and labeled sequentially. Funnel plots were used to examine the potential for publication bias. A “leave-one-out” sensitivity analysis was performed to examine the impact of excluding each study from the analysis one at a time to identify studies that might have skewed the results. Meta-regression was used to examine heterogeneity by baseline SBP.

Cost-Effectiveness Analysis

Model overview.

The BP Control-CVD Policy Model (BP-CVDPM) is a hybrid, discrete event simulation model combining the independently validated BP Control Model and CVD Policy Model ( Figure S1 ). 10 The BP-CVDPM predicts long-term BP outcomes by simulating modifiable hypertension care management processes and subsequent effect on CVD events, direct healthcare costs, survival, and quality-adjusted survival ( Supplemental Methods ).

The model simulated a nationally representative cohort of 100,000 US adults (aged ≥20 years) with uncontrolled BP (SBP/DBP ≥140/90 mmHg) identified from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 cycles. Included individuals from NHANES had lifetime CVD risk factor trajectories multiply imputed from participants in the National Heart, Lung, and Blood Institute Pooled Cohorts Study ( Supplemental Methods ). 10 - 14

Comparators

In the primary analysis, three strategies were compared: usual care, TBC with physician antihypertensive medication titration, and TBC with non-physician antihypertensive medication titration ( Table S2 ). The usual care strategy was the same as previously published. 7 , 10 , 15 All TBC visits were assumed to be in addition to usual care visits. For TBC with physician antihypertensive medication titration, it was assumed individuals had TBC visits with a registered nurse where BP was measured and hypertension counseling, including medication adherence, was provided. If BP was uncontrolled at these visits, it was assumed that this was communicated to the physician who then determined if treatment should be intensified. TBC visits with non-physician medication titration were assumed to be the same except that care was provided by a pharmacist who could also intensify treatment if BP was uncontrolled.

In the primary analysis, TBC visits were assumed to occur for twelve months, matching the meta-analysis; this was explored in sensitivity analysis. After TBC visits had ended, individuals were assumed to return to usual care. Both TBC arms were assumed to have beneficial effects on medication adherence ( Supplemental Methods ), which decreased linearly over one year after the end of TBC visits until no adherence benefits over usual care remained. 10 , 15

Model Inputs

In the primary analysis, the frequency of physician office visits (once every 11.5 weeks) and TBC visits (once every six weeks) matched the frequency from the meta-analysis intervention during the first twelve months ( Table 1 ). After the first twelve months, TBC visits ended, and usual care visit frequency was dependent upon BP control and patient and visit characteristics. 7 , 10

Selected BP-CVDPM team-based care inputs.

BP – blood pressure, CKD – chronic kidney disease, SBP – systolic blood pressure, TBC – team-based care, USD – United States dollars.

Notes: The table shows the mean base-case values, and the upper and lower values used in sensitivity analysis, for selected model inputs related to the TBC interventions.

Costs for TBC visits were calculated using the national median hourly wage for registered nurses and pharmacists, derived from the US Bureau of Labor Statistics, and duration of the visit derived from interviews with providers in prior analyses, and an assumed 30% rate for the cost of employee benefits ( Table 1 ). 10 , 16 , 17 For TBC with physician titration, an additional cost was added for physicians to review notes and determine if treatment intensification was needed using (CPT code: 99211). All other model inputs, including other costs, were derived from published literature and analysis of publicly available databases ( Table S3 ).

The primary outcomes were total direct healthcare costs (2021 USD), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) at 10 years from a healthcare sector perspective. 18 All future costs and QALYs were discounted 3% annually. 18 TBC was classified as highly cost-effective when the ICER was <$50,000 per QALY gained and at least intermediately cost-effective when <$150,000 per QALY gained. 19 Secondary outcomes included CVD events, survival, SBP changes, proportion with controlled BP (<140/90 mmHg), disaggregated costs, and disaggregated QALYs.

As in prior analyses, the BP-CVDPM was calibrated to match contemporary US CVD event and mortality rates and reproduce the difference in SBP with TBC interventions vs. usual care at six and twelve months from the meta-analysis ( Supplemental Methods , Figures S2 - S3 , Table S4 ). 10 - 12 , 15 The analyses adhered to practices recommended in the Consolidated Health Economic Evaluation Reporting Standards ( Table S5 ). 20 The BP-CVDPM was programmed in TreeAge Pro 2021 (TreeAge Software Inc, Williamstown, MA) with additional analyses performed using R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria). To ensure stable cost-effectiveness estimates, 100,000 individuals were simulated in all analyses. The mean and uncertainty interval (UI) for all outcomes were derived from 100 probabilistic iterations, where input parameters were randomly sampled from pre-specified statistical distributions. Uncertainty in the ICER was reported as the proportion of iterations with an ICER <$50,000 and <$150,000 per QALY gained.

Sensitivity Analyses

One-way sensitivity analyses were used to examine the effect of independently varying the model inputs shown in Table 1 across plausible ranges on the cost-effectiveness of TBC, while holding all other inputs at their base-case values ( Supplemental Methods ). Additional analyses examined the impact of extending the duration over which TBC visits occurred to 5 and 10 years, with the same visit frequency as occurred in the first year. Separately, a “light touch” scenario was simulated in which individuals only had one TBC visit per year after the initial twelve months with 5- and 10-year durations of TBC visits. As costs beyond those required to directly provide patient care may be incurred with TBC, a scenario analysis included administrative costs of TBC ( Supplemental Methods ). 10

A total of 19 studies were identified from the prior meta-analyses and updated literature search, comprising 5,993 individual participants ( Figure S4 ). 17 , 21 - 39 The mean (SD) baseline age was 58.9 (6.8), 35.3% were female, 37.7% were Black, and mean baseline SBP was 148.1 (10.3) mmHg ( Tables S6 - S7 ). The components included in TBC (e.g., web-based communications, self-monitoring of BP) and workflow for hypertension management varied across trials ( Table S7 ). The overall risk of bias was rated as low in 63% of the studies, some concerns of bias in 32%, and high in 5% ( Figure S5 ).

A total 12 studies (3,322 participants) and 7 studies (3,128 participants) were included in the meta-analyses of SBP change at six and twelve months, respectively. At six and twelve months, TBC overall had 7.2 mmHg (95% confidence interval [CI] −10.6, −3.8) and 8.1 mmHg (95% CI −12.1, −4.1) greater reductions in SBP than usual care ( Figure 1 ), respectively. SBP reductions vs. usual care varied by the team member titrating antihypertensive mediations; physician titration resulted in 4.7 mmHg (95% CI −8.1, −1.4) and 5.0 mmHg (95% CI −7.9, −2.2) greater reductions, and non-physician titration in 11.5 mmHg (95% CI −15.7, −7.4) and 10.5 mmHg (95% CI −16.2, −4.8) greater reductions, at six and twelve months, respectively.

A) Six months

B) Twelve months

WMD – weighted mean difference.

Notes: The figure shows the results of the meta-analysis for the change in systolic blood pressure for team-based care vs. usual care at 6 months in Panel A and 12 months in Panel B .

The results for DBP and BP control followed the same patterns as SBP ( Figures S6 - S7 ). For the outcomes of SBP change and BP control at 6 months, there did not appear to be evidence of publication bias. However, for other outcomes, asymmetry in the funnel plots was observed ( Figure S8 ). The “leave-one-out” sensitivity analysis indicated the SBP reduction at twelve months for TBC with non-physician titration was sensitive to the inclusion of the Victor et al. 2019 study, decreasing to −8.3 mmHg (95% CI −10.3, −6.3) when removed ( Figure S9 ). 17 The meta-regression showed that greater reductions in SBP at six and twelve months with TBC vs. usual care were associated with higher baseline SBP ( Figure S10 ).

Cost-effectiveness

Primary analysis.

The mean (SD) baseline age of the simulated population of US adults with uncontrolled hypertension was 59.7 (16.4) years, 50.1% were female, and mean baseline SBP was 150.6 (14.3) mmHg ( Table S8 ). At 10 years, the mean SBP with usual care was projected to be 137.9 (95% UI 136.6, 139.9) mmHg; twelve months of TBC was estimated to reduce SBP relative to usual care at 10 years by 0.8 (95% UI −1.0, −0.7) mmHg with physician titration and 3.3 (95% UI −3.9, −2.6) mmHg with non-physician titration ( Figure 2 , Table 2 ). TBC was estimated to reduce the number of individuals with ≥1 CVD event by 5 (95% UI 3, 8) per 1000 treated with physician titration and 11 (95% UI 8, 14) with non-physician titration.

A) Projected systolic blood pressure over time

B) Incremental costs and quality-adjusted life years vs. usual care

C) Cost-effectiveness acceptability curve

QALY – quality-adjusted life years, SBP – systolic blood pressure, TBC – team-based care, USD – United States dollars.

Notes: The figure shows the projected changes in SBP with each strategy over the simulated time horizon in Panel A , the incremental costs and incremental QALYs for TBC vs. usual care in Panel B , and the probability of TBC and usual care being the preferred strategy as the cost-effectiveness threshold is varied in Panel C . The shaded region in Panel A shows the 95% uncertainty interval from 100 probabilistic iterations of the model.

Clinical and cost-effectiveness outcomes at 10 years.

BP – blood pressure, CVD – cardiovascular disease, ICER – incremental cost-effectiveness ratio, QALY – quality-adjusted life year, Ref – reference group, SBP – systolic blood pressure, TBC – team-based care, USD – United States dollars.

Notes: The table shows the projected clinical and economic outcomes of usual care, TBC with physician titration of medications, and TBC with non-physician titration of medications at 10 years. TBC was assumed to occur during the first year of the simulation. After the first year, hypertension care processes (e.g., visit frequency, probability of medication titration, medication adherence) were assumed to return to usual care. Values are mean and 95% uncertainty interval (2.5th to 97.5th percentile) derived from 100 probabilistic iterations of 100,000 individuals.

The estimated per-patient cost for TBC visits over twelve months was $373 (95% UI $369, $378) with physician titration and $231 (95% UI $226, $235) with non-physician titration. Relative to usual care at 10 years, TBC with non-physician titration was estimated to cost $4,400/QALY gained and was the preferred strategy in 100% of model iterations at a cost-effectiveness threshold of <$50,000/QALY gained ( Figure 2 ). TBC with non-physician titration was estimated to dominate (i.e., cost less and be more effective) TBC with physician titration in 30% of probabilistic analyses.

Sensitivity Analysis

The cost-effectiveness of TBC with non-physician titration was most sensitive to the probability of non-physician medication titration when BP was uncontrolled and frequency of TBC visits ( Figure S11 ). Relative to usual care, TBC with non-physician titration remained highly cost-effective even with only one TBC visit every 12 weeks. In the scenario analyses with increased duration of TBC to 5 and 10 years, TBC with physician titration continued to be dominated by TBC with non-physician titration, which was highly or intermediately cost-effective vs. usual care ( Table S9 ). In the “light touch” scenarios with 5 and 10 years of TBC but with only one visit per year in subsequent years, TBC with non-physician titration continued to be highly cost-effective relative to usual care. In the scenario analysis including administrative costs, TBC with non-physician titration remained highly cost-effective with an ICER $17,400/QALY gained and continued to dominate TBC with physician titration. If TBC with non-physician titration could be implemented for <$1,100 or <$3,300 per patient enrolled, it would remain highly or intermediately cost-effective, respectively.

Hypertension TBC with a non-physician team member (e.g., pharmacist) titrating antihypertensive medications yields better BP outcomes than usual care or TBC with physician medication titration. Additionally, TBC with a non-physician team member titrating medications is highly cost-effective vs. usual care (ICER $4,400/QALY gained) and is estimated to cost less and be more effective than TBC with physician titration. Health care organizations that have capacity to deploy non-physicians to titrate antihypertensive medications as part of a TBC program may face up-front implementation costs, but our analysis suggests that this approach will yield health and economic value over time.

The greater BP reduction with TBC with non-physician medication titration that we estimated is consistent with prior meta-analyses upon which our analysis expanded. 5 , 6 Few prior economic analyses have estimated the impact of TBC for hypertension management. One analysis of US adults estimated that 1-year of hypertension TBC delivered by a pharmacist or nurse would decrease SBP by 8.1 mmHg relative to usual care at a per-patient cost of $1,046 (inflated to 2021 USD) for office and telephone visits. 40 Another analysis of a pharmacist-led home BP telemonitoring intervention found a decrease in SBP by 9.7 mmHg relative to usual care at 1 year with a total per-patient cost of $1,457 (inflated to 2021 USD). This estimate did not substantially differ from usual care costs and included pharmacist visits, telemonitoring costs, and savings in medical care but did not include longer-term projections or impact on quality of life. 35 , 41 The current study builds upon these analyses by estimating the impact of varying the processes of care driving changes in BP, which may be useful for health systems in designing and implementing TBC that fits into existing frameworks.

Healthcare systems are often reimbursed relative to their success in controlling BP, among other quality metrics, introducing financial incentives to optimize care delivery. Our analysis indicates that use of non-physician team members with the ability to prescribe and titrate antihypertensive medications, e.g., clinical pharmacists under a collaborative practice agreement, may improve BP and CVD outcomes in a cost-effective manner. However, health systems may encounter barriers to implementing these programs in a sustainable fashion due to challenges with team member availability, variability in state laws allowing collaborative practice agreements between physicians and pharmacist, insufficient reimbursement for pharmacist services, and high upfront training and implementation costs. However, successful TBC programs demonstrate that these obstacles can be overcome. 35 , 42 , 43 With persistent decline in BP control rates on a national scale and disruptions to care because of the COVID-19 pandemic, establishing a framework for TBC for hypertension control is imperative to improve CVD outcomes.

This work is strengthened by use of the BP-CVDPM and the ability to simulate processes of hypertension care that drive changes in BP. However, these results should be considered in the context of the following limitations. There is a lack of representation of racial and ethnic minority populations in the original trials, as most studies in our meta-analysis had a majority white population, with few exceptions. 17 , 27 Additionally, the impacts of social determinants of health were not captured in our analysis. We were therefore unable to explore TBC designs that account for different outcomes that may result from differences in access to care, affordable medications, adequate nutrition, and safe, stable environments. Future research should examine the impact of these factors and how TBC may be implemented in ways that promote health equity and decrease disparities. 44 Cost data from individual trials were not available, trials may not have intended to perform cost-effectiveness analyses, and cost-effectiveness components were not necessarily systematically reported; therefore, national estimates were used in our analysis. Though our analysis indicates TBC with a non-physician who can titrate medications improves BP control, detailed workflows and intervention components (e.g., inclusion of self-monitoring of BP) varied across trials and their contribution to BP lowering with TBC were not assessed in our analysis. Meta-analyses show the intensity of a self-monitoring of BP intervention is positively associated with BP lowering. 8 There may be a synergistic effect on BP lowering achieved by combining TBC with self-monitoring of BP. 8 , 15 As uptake of self-monitoring increases both because of improved guideline adherence and transition to and persistence of telemedicine in the wake of the COVID-19 pandemic, more data are likely to be available to better understand the impact of self-monitoring of BP on TBC.

This work was conducted from a healthcare sector perspective, which includes direct healthcare costs regardless of the payer, and used national averages for costs of providers and medications, which may not be applicable to local health systems. Training and licensing costs for non-physicians were not included and other costs of implementing TBC (e.g., time for scheduling TBC visits, BP measurement equipment) may not be fully accounted for in our analysis. However, incorporating administrative costs for TBC in our analysis did not alter cost-effectiveness conclusions.

NOVELTY AND RELEVANCE

What is new.

• Hypertension care provided by a team of providers that includes a non-physician who can titrate antihypertensive medications cost-effectively reduces systolic blood pressure and cardiovascular disease risk

What Is Relevant?

• Hypertension control has worsened in the US over the last decade and team-based care is recommended by hypertension treatment guidelines to improve control

Clinical Implications?

• Health systems providing team-based care for hypertension should prioritize inclusion of non-physician providers who can titrate antihypertensive medications

PERSPECITVES

TBC with non-physician titration is a clinically effective and cost-effective strategy to improve hypertension control and help reverse the current national trends. These results should be used to inform policy with the potential to restructure reimbursement to facilitate implementation. Clinics and health systems actively implementing TBC can use these results to guide program design.

Supplementary Material

Supplemental material, acknowledgements.

This work would not have been possible without the original trial participants and dedicated researchers.

SOURCES OF FUNDING

This analysis was funded by R01HL130500 (Dr. Moran) and K01HL140170 (Dr. Bellows) from National Heart, Lung, and Blood Institute (NHLBI; Bethesda, MD). Additionally, Dr. Kronish was supported by R01HL152699, Dr. Fontil was supported by K23HL136899, and Dr. Zhang was supported by R01HL158790, both from the NHLBI (Bethesda, MD). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, approval of the manuscript; or decision to submit for publication.

NON-STANDARD ABBREVIATIONS

DISCLOSURES

The meta-analysis was not prospectively registered.