Multidimensional frailty is strongly associated with syncope in older adults. Our findings reveal that differences between patients who experienced one or more episodes of syncope and those who never had a syncopal episode are primarily notable among subjects with a high degree of multidimensional frailty. Specifically, in patients with a history of syncope, dependence in ADLs, cognitive decline, polypharmacy, and low physical performance status are more pronounced.
Syncope is highly prevalent in older adults [7]. Age-related changes in blood pressure control increase the susceptibility to syncope in older adults. Baroreflex sensitivity is blunted by aging, resulting in a reduced heart rate and vasoconstriction response to hypotensive stimuli [23]. Furthermore, older patients are prone to dehydration and reduced blood volume due to a decreased thirst sensation, a reduction in renin–aldosterone activity, and a decreased capacity of the kidney to preserve salt and water [24]. Co-morbidities and concomitant medication can further impair the adaptive response to hypotensive stress. Prolonged bed rest is common in older and frail patients, often leading to syncope when they sit up [25]. The burden of age-related neuro-autonomic changes, comorbidities, and polypharmacy can be identified through multidimensional frailty evaluation, which should be considered a valuable tool in managing older adult patients with syncope.
Despite the extensive literature on syncope in older adults, there are limited data regarding the role of frailty in syncope. In a small case–control study, Bandhu et al. analyzed the association of recurrent cardiovascular syncope with various geriatric syndromes, demonstrating that syncope was significantly associated with cognitive impairment, hearing impairment, frailty, and the presence of four or more comorbidities. However, in multivariate analysis, significant associations of syncope were only observed with cognitive impairment, hearing impairment, and the presence of four or more comorbidities. This study primarily included patients with recurrent syncope of cardiac origin, which represents only a fraction of older patients with syncope [26].
Although the prevalence of cardiac disease rises dramatically with age, the relative prevalence of cardiac syncope does not show increase with age, remaining around 15%, probably due to the survival bias associated with the high mortality of cardiac syncope [27]. Of particular interest is the observation that in previous studies evaluating the characteristics of syncope type in relation to age, there is a relative reduction in cases of reflex syncope and an increase in those due to OH in older patients [28]. In the GIS study, when comparing patients younger than 75 years to those older than 75, reflex syncope (including vasovagal syncope, situational syncope, and carotid sinus syndrome) was more common in younger patients (60% vs. 35%), whereas OH syncope was more frequent in older ones (35% vs. 10%) [29]. In older patients with dementia from the SYD study, OH was the main form of syncope, accounting for about 50% of cases [30].
Our study results are consistent with these findings. Specifically, as the degree of frailty increases, the relative percentage of reflex syncope events decreases (light and moderate frail: ~ 40% vs. severe frail: ~ 35%), while the relative percentage of OH syncope increases (light and moderate frail: ~ 20% vs. severe frail: ~ 27%). Taken together, these data suggest that frailty, a condition closely associated with aging, may be a major determinant in the changing etiology of syncope with advancing age. Our research group has also previously established that frailty is a significant marker of OH, which is the primary pathophysiological mechanism underlying syncope in older patients [31].
However, in our study, multidimensional frailty is associated with an increased incidence of all forms of syncope except cardiac syncope. This result underscores the close link between frailty and non-cardiac syncope, potentially highlighting the importance of frailty as a marker of the “vasodepressive phenotype” of syncope [32]. Analysis of tilt-table tests across different age groups shows that the prevalence of vasodepressive responses increases with age, while cardioinhibitory responses decrease, suggesting an age-related decline in the cardioinhibitory component of reflex syncope [33]. This shift likely results from diminished cardiovascular autonomic control, including reduced baroreceptor sensitivity, decreased cardiac response to beta-adrenergic stimulation, and lower vagal drive to the heart [34]. Thus, older adults seem to be more prone to develop neuro-cardiovascular instability and vasodepressive reflex syncope. Additionally, hypotensive medications and comorbidities may further contribute to vasodepressive status in older patients [35].
A significant finding in our results is the close association between the percentage of syncope of “unknown origin” and the degree of multidimensional frailty. This finding is crucial as it underscores the diagnostic challenges in evaluating syncope in older population. Previous studies have demonstrated that adopting a structured and validated diagnostic protocol reduces the percentage of unexplained syncope in older adults even in a challenging population such as older patients with dementia [30]. Our study highlights that the critical factor is the degree of frailty, rather than age or cognitive decline, leading to an inconclusive diagnostic pathway in one out of four syncope cases (10% in light frailty vs. 24.5% in severe frailty). Many factors may be involved in this matter, such as the difficulty in performing neuro-autonomic assessment tests or in reporting anamnestic elements that can be crucial in the correct framing of the episode [36].
Moreover, our analysis indicates that all domains of multidimensional frailty significantly impact the likelihood of syncopal events. Social isolation can result in a lack of support systems, thereby reducing the likelihood of individuals receiving assistance during pre-syncopal or syncopal events, which may increase the severity of the outcomes [37]. Limited access to healthcare, social services, and community support further exacerbates the underlying factors contributing to frailty and syncope [38]. Furthermore, nutritional risk, associated with dehydration, labile blood pressure values, and OH, constitutes an additional significant risk factor for syncopal events [39].
To our knowledge, this is the first study specifically focused on the relationship between syncope and multidimensional frailty in older adults. One of the major strengths of our research lies in the rigorous and methodologically robust assessment of frailty and syncope. Frailty was evaluated by ensuring a comprehensive and multidimensional approach. Syncope assessment adhered strictly to the European Society of Cardiology guidelines, with detailed diagnostic workups conducted in specialized Syncope and Falls Units. This methodological rigor significantly enhances the reliability of our findings.
However, it is important to acknowledge certain limitations. The retrospective design of our study may introduce potential biases. Notably, as many patients were referred to outpatient centers equipped with dedicated Syncope and Falls Units, the observed incidence of syncope could be elevated compared to the general population of older adults. Additionally, the recruitment of participants exclusively from a single Italian region may limit the generalizability of our results. Future studies should consider incorporating a prospective design and expanding the sample to include more diverse demographic groups. Moreover, exploring interventions aimed at reducing frailty could provide valuable insights into mitigating syncope risks in this population. Such approaches would not only validate our findings but also deepen our understanding of the interactions between frailty and syncope, potentially guiding more effective clinical strategies.