The relation between age, sex, comorbidity, and pharmacotherapy and the risk of syncope: a Danish nationwide study
Open accessAbstract
AIMS: Syncope is a common cause for hospitalization and may be related to comorbidity and concurrent medication. The objective of this study was to determine the incidence, comorbidity, and pharmacotherapy in a nationwide cohort of patients hospitalized with syncope. METHODS AND RESULTS: An observational study including patients with the diagnosis of syncope identified from the Danish National Patient Register in the period 1997-2009. All patients were matched on sex and age with five controls from the Danish population. We estimated the incidence of syncope and the association with comorbidities and pharmacotherapy by conditional logistic regression analyses. We identified 127 508 patients with a first-time diagnosis of syncope [median age 65 years (interquartile range 49-81), 52.6% female]. The age distribution of the patients showed three peaks around 20, 60, and 80 years of age with the third peak occurring 5-7 years earlier in males. Cardiovascular disease and cardiovascular drug therapy was present in 28 and 48% of the patients, respectively. We found significant association between cardiovascular disease and the risk of admission for syncope increasing with younger age; age 0-29 years [odds ratio (OR) = 5.8, confidence interval (CI): 5.2-6.4), age 30-49 (OR = 4.4, CI: 4.2-4.6), age 50-79 (OR = 2.9, CI: 2.8-3.0), and age above 80 (OR = 2.0, CI: 1.9-2.0). Cardiovascular pharmacotherapy associated with age and risk of syncope was similar. CONCLUSION: In a nationwide cohort of patients hospitalized for first syncope we found significant association between cardiovascular comorbidity and pharmacotherapy and the risk of syncope. The occurrence of syncope displayed an age distribution with important gender-specific differences and higher incidence rates than previously reported.
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The incidence of syncope follows a trimodal distribution in both sexes, with the first episode common around 20, 60, or 80 years of age and the third peak occurring 5 to 7 years earlier in males.
“The incidence follows a trimodal distribution in both sexes, with the first episode common around 20, 60, or 80 years of age and the third peak occurring 5 to 7 years earlier in males (45).”
From 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope (2017) · cites this paper as [45]
The “Age and gender incidence rates of syncope” section says incidence rates were bimodal, contrary to the claimed trimodal incidence. The “Age and gender distribution of syncope” section does report three peaks in the patients’ age distribution around 20, 60, and 80 years, with the third peak 5–7 years earlier in males. The claim conflates that age distribution with incidence rates. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredPredictors of recurrent syncope in older adults are aortic stenosis, impaired renal function, AV or left bundle-branch block, male sex, chronic obstructive pulmonary disorder, heart failure, atrial fibrillation, advancing age, and orthostatic medications.
“Predictors of recurrent syncope in older adults are aortic stenosis, impaired renal function, atrioventricular (AV) or left bundle-branch block, male sex, chronic obstructive pulmonary disorder, heart failure (HF), atrial fibrillation (AF), advancing age, and orthostatic medications (45), with a sharp increase in incidence after 70 years of age (35).”
From 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope (2017) · cites this paper as [45]
Table 1 and the Multivariate logistic regression analyses associate several listed comorbidities and cardiovascular medications with syncope. But the study examines first-time syncope admissions, not predictors of recurrence in older adults; it does not identify aortic stenosis or the specified block types as predictors. The Age and gender incidence rates section reports higher incidence in women than men, and Table 3 does not show increased adjusted odds for heart failure in the older age groups. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe diagnosis of syncope in older adults is imprecise because of amnesia, falls, lack of witnesses, and polypharmacy.
“The management of syncope in older adults is particularly challenging: The incidence is high; the differential diagnosis is broad; the diagnosis is imprecise because of amnesia, falls, lack of witnesses, and polypharmacy; and secondary morbidity is high because of comorbidities, physical injury, and frailty (35,45,666–675).”
From 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope (2017) · cites this paper as [45]
The Introduction says that differentiating causes of syncope is challenging, and the Implications section recommends considering concomitant medication during evaluation. Neither section says that diagnosis in older adults is imprecise because of amnesia, falls, lack of witnesses, or polypharmacy; the paper’s mention of recollection bias in elderly participants concerns incidence estimates, not diagnosis. Page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredSecondary morbidity from syncope in older adults is high because of comorbidities, physical injury, and frailty.
“The management of syncope in older adults is particularly challenging: The incidence is high; the differential diagnosis is broad; the diagnosis is imprecise because of amnesia, falls, lack of witnesses, and polypharmacy; and secondary morbidity is high because of comorbidities, physical injury, and frailty (35,45,666–675).”
From 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope (2017) · cites this paper as [45]
The Introduction (page unavailable) links syncope to possible physical harm and associates poor outcomes with the severity of underlying disease. The Conclusion describes substantial comorbidity among patients with syncope, including older patients. The paper does not establish that secondary morbidity is high specifically in older adults or attribute it to frailty. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAn increased probability of developing multiple concurrent morbidities (with their associated pharmacological treatments) that can overwhelm homeostasis increases vulnerability of older adults to syncope.
“The vulnerability of older adults to syncope increases because of age-associated cardiovascular and autonomic changes, decreased fluid conservation (45,671,676–678), and an increased probability of developing multiple concurrent morbidities (with their associated pharmacological treatments) that can overwhelm homeostasis.”
From 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope (2017) · cites this paper as [45]
The Discussion and Conclusion (page unavailable) report that syncope is more common in older people and is associated with cardiovascular comorbidity and pharmacotherapy. But the Implications section explicitly says the study cannot establish causality; it does not show that multiple concurrent conditions and their treatments overwhelm homeostasis or thereby increase older adults’ vulnerability. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Age-associated cardiovascular and autonomic changes increase vulnerability of older adults to syncope.
“The vulnerability of older adults to syncope increases because of age-associated cardiovascular and autonomic changes, decreased fluid conservation (45,671,676–678), and an increased probability of developing multiple concurrent morbidities (with their associated pharmacological treatments) that can overwhelm homeostasis.”
From 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope (2017) · cites this paper as [45]
The Conclusion (page unavailable) says syncope is more common in the elderly, and the Implications section reports an association between cardiovascular disease and syncope. Neither section attributes older adults’ vulnerability to age-associated cardiovascular or autonomic changes; the Implications section explicitly says the study cannot establish causality. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe incidence of syncope in older adults is high.
“The management of syncope in older adults is particularly challenging: The incidence is high; the differential diagnosis is broad; the diagnosis is imprecise because of amnesia, falls, lack of witnesses, and polypharmacy; and secondary morbidity is high because of comorbidities, physical injury, and frailty (35,45,666–675).”
From 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope (2017) · cites this paper as [45]
The differential diagnosis of syncope in older adults is broad.
“The management of syncope in older adults is particularly challenging: The incidence is high; the differential diagnosis is broad; the diagnosis is imprecise because of amnesia, falls, lack of witnesses, and polypharmacy; and secondary morbidity is high because of comorbidities, physical injury, and frailty (35,45,666–675).”
From 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope (2017) · cites this paper as [45]
Decreased fluid conservation increases vulnerability of older adults to syncope.
“The vulnerability of older adults to syncope increases because of age-associated cardiovascular and autonomic changes, decreased fluid conservation (45,671,676–678), and an increased probability of developing multiple concurrent morbidities (with their associated pharmacological treatments) that can overwhelm homeostasis.”
From 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope (2017) · cites this paper as [45]
The Introduction describes syncope in older adults, and the Conclusion associates syncope with cardiovascular comorbidity and medication. Neither passage addresses decreased fluid conservation as a cause of vulnerability; searches for fluid conservation, dehydration, and related terms found no such explanation in our copy. (LLM, conf=0.76)
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2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope
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Epidemiology of Syncope/Collapse in Younger and Older Western Patient Populations
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Self-citationAF is associated with self-reported syncope and falls in a general population cohort
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- Authors
- Ruwald, M. H., Hansen, M. L., Lamberts, M., Hansen, C. M., Hojgaard, M. V., Kober, L., Torp-Pedersen, C., Hansen, J., & Gislason, G. H.
- Affiliations
- Gentofte Hospital (DK)
- Corresponding author
- Ruwald, M. H.
- Venue
- Europace
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-05-15
- Volume
- 14
- Issue
- 10
- Pages
- 1506-1514
- ISSN
- 1099-5129 (ISSN-L)
- 1532-2092
- OpenAlex
- W2171842148
- Cited by
- 118
- References
- 1
- Citations by year
- 2026: 10 · 2025: 7 · 2024: 7 · 2023: 6 · 2022: 7 · 2021: 9 · 2020: 5 · 2019: 3 · 2018: 13 · 2017: 17 · 2016: 6 · 2015: 5 · 2014: 11 · 2013: 10 · 2012: 2
- FWCI
- 9.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- EP Europace (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Health Sciences › Health Professions › Physical Therapy, Sports Therapy and Rehabilitation › Balance, Gait, and Falls Prevention
- Keywords
- syncope, cardiovascular comorbidity, cardiovascular pharmacotherapy, age distribution, sex differences, hospitalization, antihypertensive drugs, antiplatelet agents
- MeSH terms
- Adult, Aged, Aged, 80 and over, Cardiovascular Agents, Cardiovascular Diseases, Denmark, Female, Hospitalization, Humans, Male, Middle Aged, Registries, Risk, Sex Factors, Syncope, Cohort Studies, Comorbidity, Incidence, Treatment Outcome, Young Adult
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