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Original Investigation
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April 22, 2024

Antihypertensive Medication and Fracture Risk in Older Veterans Health Administration Nursing Home Residents

Author Affiliations
  • 1Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey
  • 2Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey
  • 3Department of Veterans Affairs-New Jersey Health Care System, East Orange
  • 4Geriatric Research Education and Clinical Center, VA Palo Alto Health Care System, Palo Alto, California
  • 5Department of Epidemiology and Population Health, School of Medicine, Stanford University, Stanford, California
  • 6Division of Geriatrics, Department of Medicine, University of California San Francisco, San Francisco
  • 7Geriatrics, Palliative, and Extended Care Service Line, San Francisco VA Medical Center, San Francisco, California
  • 8Health Economics Resource Center, VA Palo Alto Health Care System, Palo Alto, California
  • 9Department of Pharmacy, University of Washington, Seattle
JAMA Intern Med. 2024;184(6):661-669. doi:10.1001/jamainternmed.2024.0507
Key Points

Question  Is initiating antihypertensive medication associated with increased fracture risk among older long-term Veterans Health Administration nursing home residents?

Findings  In a 1:4 propensity score–matched cohort of 64 710 residents, initiation of antihypertensive medication was associated with increased fracture risk and adjusted excess risk per 100 person-years. This risk was numerically higher in subgroups of residents with dementia or with systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 80 mm Hg or higher.

Meaning  Findings from this cohort study suggest that caution and additional monitoring are advised when initiating antihypertensive medication in this vulnerable population.

Abstract

Importance  Limited evidence exists on the association between initiation of antihypertensive medication and risk of fractures in older long-term nursing home residents.

Objective  To assess the association between antihypertensive medication initiation and risk of fracture.

Design, Setting, and Participants  This was a retrospective cohort study using target trial emulation for data derived from 29 648 older long-term care nursing home residents in the Veterans Health Administration (VA) from January 1, 2006, to October 31, 2019. Data were analyzed from December 1, 2021, to November 11, 2023.

Exposure  Episodes of antihypertensive medication initiation were identified, and eligible initiation episodes were matched with comparable controls who did not initiate therapy.

Main Outcome and Measures  The primary outcome was nontraumatic fracture of the humerus, hip, pelvis, radius, or ulna within 30 days of antihypertensive medication initiation. Results were computed among subgroups of residents with dementia, across systolic and diastolic blood pressure thresholds of 140 and 80 mm Hg, respectively, and with use of prior antihypertensive therapies. Analyses were adjusted for more than 50 baseline covariates using 1:4 propensity score matching.

Results  Data from 29 648 individuals were included in this study (mean [SD] age, 78.0 [8.4] years; 28 952 [97.7%] male). In the propensity score–matched cohort of 64 710 residents (mean [SD] age, 77.9 [8.5] years), the incidence rate of fractures per 100 person-years in residents initiating antihypertensive medication was 5.4 compared with 2.2 in the control arm. This finding corresponded to an adjusted hazard ratio (HR) of 2.42 (95% CI, 1.43-4.08) and an adjusted excess risk per 100 person-years of 3.12 (95% CI, 0.95-6.78). Antihypertensive medication initiation was also associated with higher risk of severe falls requiring hospitalizations or emergency department visits (HR, 1.80 [95% CI, 1.53-2.13]) and syncope (HR, 1.69 [95% CI, 1.30-2.19]). The magnitude of fracture risk was numerically higher among subgroups of residents with dementia (HR, 3.28 [95% CI, 1.76-6.10]), systolic blood pressure of 140 mm Hg or higher (HR, 3.12 [95% CI, 1.71-5.69]), diastolic blood pressure of 80 mm Hg or higher (HR, 4.41 [95% CI, 1.67-11.68]), and no recent antihypertensive medication use (HR, 4.77 [95% CI, 1.49-15.32]).

Conclusions and Relevance  Findings indicated that initiation of antihypertensive medication was associated with elevated risks of fractures and falls. These risks were numerically higher among residents with dementia, higher baseline blood pressures values, and no recent antihypertensive medication use. Caution and additional monitoring are advised when initiating antihypertensive medication in this vulnerable population.

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6 Comments for this article
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Very Plausible Results
David Karpf, ND | Stanford University School of Medicine
I read with interest the report "Antihypertensive Medication and Fracture in in Older Veterans Health Administration Nursing Home Residents".

For a non-RCT, the methodology utilized by the authors provides pretty compelling and entirely plausible results, that adding a BP med or initiating a BP med in an older population of nursing home residents increases the risk of falls, and hence fractures (as well as probably brain trauma and mortality, via the probably mechanism of orthostatic hypotension.

While I follow a large population of patients with osteoporosis (but almost completely lacking dementia or benzodiazepine use or other risk factors),
and ALWAYS stress the importance of fall prevention, this population of veterans comprises a particularly vulnerable population of patients at increased risk of falls and fractures. The results of this study highlights the importance of elevating the importance of fall prevention in nursing homes, especially in patients recently started on anti-hypertensive therapy.

David B. Karpf, MD
Adj. Clinical Professor of Endocrinology
Stanford University School of Medicine
Attending, Osteoporosis & Metabolic Bone Disease Clinic
Stanford University Hospital & Clinics

Fellow, ASBMR
CONFLICT OF INTEREST: None Reported
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Measurement errors contributing to overtreatment
Steven Yarows, MD | IHA Trinity
I want to thank the authors for this very important research concluding the dangerous of anti-hypertension overtreatment in this frail population. I postulate that mismeasurement of the blood pressure contributed to the overtreatment with medication. This has been reported for the hospitalized population resulting in increased ICU admissions and acute kidney failure. Most nursing home measurements are not performed with the patient sitting in a chair for 5 minutes prior to measurements. Supine blood pressures and measurements without a proper rest period result in artificial elevated readings which can lead to overtreatment and injury. Repeated proper measurements over days to weeks before increasing anti-hypertensive treatment may prevent increased falls and injuries.
CONFLICT OF INTEREST: None Reported
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Over treatment - causes harm
Arun Tandon |
Antihypertensive use to bring BP to 120/80, in Elderly is a sure way to increase fall risk. Keep BP a little higher so the elderly have enough strength to get up and go.
CONFLICT OF INTEREST: None Reported
RE: Antihypertensive medication and fracture risk in older Veterans Health Administration nursing home residents
Tomoyuki Kawada, MD | Nippon Medical School
Dave et al. conducted a retrospective cohort study to evaluate the initiation of antihypertensive medication on the risk of fractures in older long-term nursing home residents (1). The adjusted hazard ratio (HR) (95% confidence interval [CI]) of antihypertensive medication for fractures was 2.42 (1.43-4.08). In addition, the adjusted HRs (95% CIs) of antihypertensive medication for severe falls and syncope were 1.80 (1.53-2.13) and 1.69 (1.30-2.19), respectively. In cases of dementia, systolic blood pressure of 140 mm Hg or higher, diastolic blood pressure of 80 mm Hg or higher, the adjusted HRs (95% CIs) were 3.28 (1.76-6.10), 3.12 (1.71-5.69), and 4.41 (1.67-11.68), respectively. The authors also reported that the adjusted HR (95% CI) of no recent antihypertensive medication use for fractures was 4.77 (1.49-15.32). I suspect that hypertension itself has a risk of fracture, and the level of management for hypertension may closely related to the risk reduction in fracture. Benefits and risk of antihypertensive medications should be evaluated by considering quality of life in older residents. I present a precise information regarding the risk of antihypertensive medications on a serious fall injury, which was published at a decade ago in the same journal. Dave et al. cited this paper without precise discussion. Indeed, the large number of events with longer follow-up period may present stable estimates for the risk of fractures. But disparities in sex existed, presenting predominant male data, and retrospective cohort design would present limitation for the selection of adjusting variables.

Tinetti et al. conducted a 3-year prospective study to evaluate the effect of antihypertensive medication use on subsequent experiencing a serious fall injury in hypertensive adults older than 70 years (2). The adjusted HRs (95% CIs) of the moderate-intensity and the high-intensity antihypertensive medications for serious fall injury were 1.40 (1.03-1.90) and 1.28 (0.91-1.80), respectively. In participants with previous fall injury, the adjusted HRs (95% CIs) of the moderate-intensity and the high-intensity antihypertensive medications for serious fall injury were 2.17 (0.98-4.80) and 2.31 (1.01-5.29), respectively. I understand the risk of fall injury in older adults with antihypertensive medications. But the level of significance nears a statistical borderline, and the intensity of antihypertensive medications may be closely related to the progression of hypertension. I suppose that the risk reduction of a serious fall injury may also be related to other medications such as antipsychotics and the limitation in body movement, caused by several comorbidities with aging, should also be considered for the analysis. There may be no gold standard criteria for adequate blood pressure management and falls in nursing home residents. In each case, we have to consider better ways of keeping quality of life.


References
1. Dave CV, Li Y, Steinman MA, Lee SJ, Liu X, Jing B, Graham LA, Marcum ZA, Fung KZ, Odden MC. Antihypertensive medication and fracture risk in older Veterans Health Administration nursing home residents. JAMA Intern Med 2024 Apr 22. doi: 10.1001/jamainternmed.2024.0507
2. Tinetti ME, Han L, Lee DS, McAvay GJ, Peduzzi P, Gross CP, Zhou B, Lin H. Antihypertensive medications and serious fall injuries in a nationally representative sample of older adults. JAMA Intern Med 2014;174(4):588-95.
CONFLICT OF INTEREST: None Reported
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pseudohypertension, dose adjusted treatment regimens, transient increases in blood pressure
Fatih Tufan, Assoc. Prof. | Istanbul Aydin University Medical Park Florya Hospital Department of Geriatrics
I congratulate the authors for this important study. I have some contributions:
1. Pseudohypertension is relatively common in older adults. In the normal aging process, systolic blood pressure increases and diastolic blood pressure decreases. When there is a similar increase in systolic and diastolic pressures in an index case, one may consider the possibility of pseudohypertension in which antihypertensive treatment may lead to falls and syncope. The fact that increased diastolic blood pressure was associated with a numerically higher HR (4.41) compared to that related with systolic blood pressure (HR=3.12) in the present study may be relevant in this regard. />2. Many older adults have variation in their blood pressure levels within the day or between days. Deciding whether to use antihypertensive medication in a given time and adjusting the dose with respect to current blood pressure may be beneficial in such conditions. Using a routine regimen regardless of current blood pressure measurement may be harmful.
3. Some conditions like vertigo and migraine are associated with transient increases in blood pressure levels. Prescribing routine antihypertensive medications for such transient conditions may lead to hypotension and syncope.
CONFLICT OF INTEREST: None Reported
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To consider Whitecoat Hypertension and BP variability
Rajeev Gupta, MBBS;MD;DM (Cardiology) | Spectrum Medical Center, and Burjeel Royal Hospital, Al Ain, UAE
It is interesting to note that the whitecoat effect and the variability (beat-to-beat, diurnal, week-to-week, and seasonal) in BP increase with age. Before initiating or titrating the dose of antihypertensive therapy, more frequent correct readings of BP, including ambulatory blood pressure monitoring bearing in mind the greater variability of BP is very common. Moreover, elderly individuals are more prone to developing dehydration, which may lead to a fall in the BP at times markedly and rather rapidly. In a nutshell, the management of hypertension in the elderly, particularly in nursing home residents is often challenging, needing frequent monitoring and titration, at times daily.
CONFLICT OF INTEREST: None Reported
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