Introduction
Benign paroxysmal positional vertigo (BPPV) is recognized as the most prevalent episodic vestibular disorder in clinical environments.Reference Neuhauser1 Characterized by short episodes of vertigo, typically lasting less than a minute, BPPV is triggered by specific head movements such as lying down, turning over in bed, looking upwards, or bending forward.Reference von Brevern, Radtke, Lezius, Feldmann, Ziese and Lempert2 Although episodes may resolve spontaneously, they can persist for days, weeks, or months without treatment. BPPV is notorious for its tendency to recur, with around 50 per cent of patients experiencing relapses even after successful initial treatment. While generally benign and self-limiting, the episodes can significantly disrupt personal and socioeconomic well-being, as well as increasing the likelihood of falls.Reference Imai, Ito, Takeda, Uno, Matsunaga and Sekine3, Reference Sfakianaki, Binos, Karkos, Dimas and Psillas4
The American Academy of Otolaryngology Head and Neck Surgery (AAO–HNS) Foundation, along with the Bárány Society, have established guidelines for diagnosing and treating BPPV.Reference Bhattacharyya, Gubbels, Schwartz, Edlow, El-Kashlan and Fife5, Reference AlMohiza6 Various manoeuvres target different semicircular canals, and the specific nystagmus and vertigo elicited by each manoeuvre enable clinicians to identify the affected side and understand the underlying pathophysiology.Reference Lopez-Escamez, Gamiz, Fernandez-Perez and Gomez-Fiñana7–Reference Dhiman and Joshi9 Consequently, they can select the most appropriate canalith repositioning procedure. These procedures are highly effective in treating BPPV, frequently providing immediate relief to patients.Reference Parnes, Agrawal and Atlas10, Reference Chen, You, He and Zhang11
However, often by the time patients reach a vestibular clinic, their symptoms have already subsided into remission, rendering it challenging to confirm the diagnosis.Reference Hilton and Pinder12, Reference Chen and Zhang13 The clinical practice guidelines acknowledge the risk of BPPV recurrence and emphasise the importance of educating patients about this possibility. Different manoeuvres to reposition canaliths can effectively alleviate symptoms, but some patients still experience residual dizziness even after successful repositioning.Reference Hornibrook14, Reference von Brevern, Seelig, Neuhauser and Lempert15 Many studies have shown that patients with residual dizziness after repositioning manoeuvres may also suffer from unsteady gait, neck discomfort, and other symptoms, significantly affecting their daily lives.Reference Imai, Ito, Takeda, Uno, Matsunaga and Sekine3, Reference von Brevern, Seelig, Neuhauser and Lempert15, Reference Pérez, Franco, Cuesta, Aldama, Alvarez and Méndez16
To reduce the incidence of residual dizziness after repositioning manoeuvres and improve the effectiveness of these treatments, it is crucial to identify the factors influencing residual dizziness post-repositioning.Reference Ke, Ma, Jing, Diao and Yu17, Reference Korres, Balatsouras, Kaberos, Economou, Kandiloros and Ferekidis18 Additionally, it remains unclear whether lipid levels are a risk factor for residual dizziness and what role they play in the physiological mechanisms influencing residual dizziness.Reference Erdur and Evran19, Reference Ren, Li and Xia20
Based on this, the present study aims to address this research gap and based on evidence, explore the independent risk factors for residual dizziness in BPPV patients following successful repositioning manoeuvres. Additionally, to further investigate the interrelationships and possible mechanisms among various influencing factors, this study intends to examine whether different lipid-related indicators act as mediators between these risk factors and residual dizziness.Reference Thomas and Newman-Toker21
Methodology
Participants and procedures
A retrospective analysis was conducted on the clinical data of 110 patients diagnosed with BPPV and treated with repositioning manoeuvres at our hospital between January 2019 and February 2022. These patients met the diagnostic criteria outlined in the AAO–HNS 2017 Guidelines for the Diagnosis and Treatment of Benign Paroxysmal Positional Vertigo. Based on the presence or absence of residual dizziness after successful repositioning manoeuvres, the patients were divided into two groups: the residual-dizziness group (30 cases) and the no-residual-dizziness group (80 cases).
The ethical standards review for our research methodology, including its objectives and protocols, was comprehensively conducted and approved by our institution’s ethics committee. This evaluation ensured the research adhered to high ethical norms, with special emphasis on safeguarding patient confidentiality and rights. The study was carefully designed to meet ethical guidelines, maintaining the integrity and scientific validity of the results. Prior to their participation, informed consent was secured from all individuals involved in the study.
Inclusion and exclusion criteria
To maintain the integrity of our dataset, we enforced strict exclusion criteria, carefully screening and excluding patients whose written records were unclear or indistinguishable. This thorough screening process was crucial to ensure the reliability of our dataset, strengthening the basis for our later analyses and findings.
Inclusion and exclusion criteria
Patients included in the study had to meet the following criteria: (1) all patients underwent relevant examinations and met the diagnostic criteria for BPPV; (2) complete clinical data were required for this study; and (3) included patients received and successfully responded to repositioning manoeuvres.
Exclusion from the study occurred if at least one of the following conditions was met: (1) patients with malignant tumours; (2) patients with chronic renal, hepatic, cardiovascular, or autoimmune diseases; (3) patients with coexisting conditions such as Ménière’s disease, vestibular neuritis, central positional vertigo, vestibular migraine or other conditions that could potentially cause vertigo; (4) patients who received other treatments (such as medication treatment) during the course of the disease; and (5) patients with bone diseases, gynaecological diseases, thyroid diseases, or recent use of hormonal medications.
Data collection
General data and lipid-related data were collected from both groups of patients. General data, collected from questionnaires, included gender, age, body mass index (BMI), smoking status, alcohol consumption, and the presence or absence of sleep disorders, which were defined as difficulty falling asleep (taking more than 30 minutes), reduced total sleep time (< 6 hours), sleep maintenance disorders (waking up at least two times per night), early awakening, decreased sleep quality, and associated daytime functional impairment. Additionally, the presence of comorbidities, including hypertension, diabetes, and lower limb arteriosclerosis, was documented. Other collected data included the onset time (expressed as days), clinical symptoms (positional vertigo, nausea, vomiting, limb weakness, and hearing loss), whether medication treatment was administered after repositioning, dizziness handicap inventory scores before repositioning, and hospital anxiety and depression scale scores before repositioning.
The diagnostic criteria for comorbidities referred to ‘Hypertension: From Basics to Clinical Practice, From Guidelines to Practice,’ ‘2014 American Diabetes Association Guidelines: Standards of Medical Care in Diabetes,’ and ‘Guidelines for Diagnosis and Treatment of Lower Extremity Arteriosclerosis Obliterans.’ The dizziness handicap inventory consists of 25 items, with a total score range of 0–100 points, including three subscales: physical (P, 28 points), emotional (E, 36 points), and functional (F, 36 points). Each item is scored as 0 (no), 2 (sometimes), or 4 (yes), with higher scores indicating more severe vertigo symptoms. The grading standard is 0–30 points for mild impairment, 31–60 points for moderate impairment, and 61–100 points for severe impairment. The hospital anxiety and depression scale comprises 14 items divided into two subscales: hospital anxiety and depression scale-A (anxiety) and hospital anxiety and depression scale-D (depression), each with 7 items. Based on the total score, results are classified as no symptoms (0–7 points), doubtful symptoms (8–10 points), and definite symptoms (11–21 points), with higher scores indicating more severe anxiety and depression.
For physiological and biochemical indicators, 3 ml of venous blood was collected from all study subjects upon admission. The blood samples were centrifuged at 3000 rpm for 10 minutes with a centrifuge radius of 15 cm. Serum was extracted and analysed using an automatic biochemical analyser (HTSH-3800, Qingdao Han Tang Biotechnology Co., China) to measure the concentrations of serum triglycerides, total cholesterol, low density lipoprotein (LDL) cholesterol, and high density lipoprotein (HDL) cholesterol.
Statistical analysis
For the characteristics of study participants, continuous variables were expressed using the mean ± standard deviation (SD), and the means between the two groups were compared using the t-test. Categorical variables were expressed using frequency (n) and per cent, and the comparisons between groups were made using the chi-square test. Multivariate logistic regression models were performed to evaluate the risk factors for residual dizziness in BPPV patients following successful repositioning manoeuvres. Several models were constructed: Model I was adjusted for age and gender. Model II was Model I with additional adjustments for smoking status, alcohol consumption, BMI, sleep disorders, comorbidities, medication treatment, dizziness handicap inventory scores and hospital anxiety and depression scale scores. Model III was Model II with additional adjustments for lipid-related indicators, including triglycerides, total cholesterol, LDL cholesterol and HDL cholesterol. Odds ratios and 95 per cent confidence intervals (CIs) were reported and calculated.
Through regression-based mediation analyses, a detailed exploration was conducted to determine both the direct effects of statistically significant risk factors on residual dizziness and their indirect effects mediated through lipid-related indicators (triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol). This investigation resulted in three key estimations: (1) the total effect, which covers the overall relationship between statistically significant risk factors and residual dizziness, including both direct connections and those mediated by lipid-related indicators; (2) the direct effect, which isolates and clarifies the link between the statistically significant risk factors and residual dizziness; and (3) the indirect effect, which reveals the pathways where lipid-related indicators mediate the relationship between statistically significant risk factors and residual dizziness.
All statistical analyses and figures were produced using R version 4.3.2 (http://www.r-project.org). We established a significance threshold with a p-value of less than 0.05, a standard that highlights the identification of significant associations within the scope of the study framework.
Results
Within the scope of this study, 110 eligible participants were included, 80 (72.7 per cent) had no residual dizziness while 30 (27.3 per cent) had residual dizziness. The participants were 66.58±9.29 years old, the majority were male (51.8 per cent); no smoking (54.5 per cent); current drinking (56.4 per cent); without sleep disorders (61.8 per cent); without hypertension (68.2 per cent); without diabetes (53.6 per cent); with limb arteriosclerosis (52.7 per cent); with positional vertigo (57.3 per cent); without nausea (58.2 per cent); without limb weakness (59.1 per cent); without hearing loss (59.1 per cent); or without medication treatment (71.8 per cent). The age, gender, smoking status, alcohol consumption, whether suffering from diabetes or not, whether suffering from positional vertigo or not, whether suffering from vomiting or not, whether suffering from limb weakness or not, whether suffering from hearing loss or not, onset time, dizziness handicap inventory score, triglycerides, BMI showed no significant difference between the two groups. In contrast, whether suffering from limb weakness or not, whether suffering from hypertension or not, whether suffering from nausea or not, whether suffering from limb weakness or not, whether suffering from limb arteriosclerosis or not, medication treatment, dizziness handicap inventory scores, hospital anxiety and depression scale scores, total cholesterol, LDL cholesterol, HDL cholesterol are significantly different between the two groups (P < 0.05). The details are shown in Supplementary Appendix A.
Supplementary Appendix B shows the results of risk factors for residual dizziness in BPPV patients following successful repositioning manoeuvres based on three models of multivariate logistic regression analysis. According to the regression results adjusted for all confounders (Model III), only sleep disorders, medication treatment, hypertension, triglycerides, and total cholesterol were significant risk factors for residual dizziness (p < 0.05). Figure 1 is a forest plot of the subgroup analysis for each factor.
Forest plot of influencing factors for residual dizziness in BPPV patients following successful repositioning manoeuvres based on Model III. OR = odds ratio; ***p < 0.001, **p < 0.01, *p < 0.05.
The mediation analyses were conducted to explore the role of significant lipid-related indicators (triglycerides and total cholesterol) between all other significant risk factors and residual dizziness. It was found that only total cholesterol had a significant mediating effect between sleep disorders and residual dizziness (all other variable combinations had p > 0.05). Specifically, the total effect on residual dizziness was 0.539 (β (95 per cent CI): 0.539 (0.369, 0.690), p < 0.001), and the indirect effect was 0.091 (β (95 per cent CI): 0.091 (0.118, 0.088), p < 0.001). This indicates that a notable indirect effect was detected for total cholesterol, contributing to 9.1 per cent of the overall change through the mediating effect of total cholesterol. Figure 2 shows the path diagram of mediation analysis of relationship between sleep disorders, medium total cholesterol concentration and residual dizziness.
Path diagram of mediation analysis of relationship between sleep disorders, medium total cholesterol (TC) concentration and residual dizziness.
Discussion
To the best of our knowledge, this is the first study to explore the risk factors for residual dizziness in BPPV patients following successful repositioning manoeuvres and to thoroughly analyse the relationship between lipid-related indicators and residual dizziness. We found that whether suffering from limb weakness, hypertension, nausea, or limb arteriosclerosis, medication treatment, dizziness handicap inventory scores, hospital anxiety and depression scale scores, total cholesterol, LDL cholesterol, and HDL cholesterol distributions were significantly different between the groups with and without residual dizziness. Moreover, the results of the multivariate logistic regression analysis further revealed that sleep disorders, medication treatment, hypertension, triglycerides, and total cholesterol were all significant risk factors for residual dizziness (p < 0.05). Simultaneously, we further revealed the mediating effect (9.1 per cent) of total cholesterol blood concentration between sleep disorders and residual dizziness.
Our study found that the more severe the sleep disorders were before repositioning, the less effective the manoeuvre was, and the higher the probability of residual dizziness. This finding aligns with another single-centre retrospective study on sleep disorders in BPPV patients, which reported that BPPV patients experienced sleep disorders before the diagnosis of BPPV, suggesting it as a significant risk factor.Reference Xue, Wang, Meng, Zhao, Wang and Zhang22 In BPPV, the detachment and displacement of otoliths can mechanically stimulate the semicircular canal’s ampullary ridge, leading to vertigo.Reference Wu, Zhang, Zhou, Liu, Yang and Han23, Reference You, Chen, Wei, Tang, Lu and Zhang24 Regarding the potential mechanisms, some researchers have reported that dysfunction in the central nervous system increases the excitability of the trigeminal caudate nucleus, solitary tract nucleus, and vestibular nucleus, resulting in vertigo.Reference Balaban and Thayer25, Reference You, Chen, Liu, Zhang, Wang and Yang26 Others have proposed that abnormal trigeminal neurovascular pathways cause asymmetric release of neurotransmitters, such as serotonin and norepinephrine, on both sides of the vestibule, also leading to vertigo.Reference Gurvich, Maller, Lithgow, Haghgooie and Kulkarni27 Therefore, residual dizziness and sleep disorders in BPPV patients may have a bidirectional causal relationship. This finding needs further exploration in future prospective cohort studies.
Similarly, our results align with a previous meta-analysis, which suggested that hypertension and hyperlipidaemia are risk factors for the recurrence of BPPV.Reference Li, Wang, Liu, Cao, Zheng and Jing28 This implies that these factors may also contribute to residual dizziness in BPPV patients even after successful repositioning manoeuvres. Our findings support this view, showing that higher levels of triglycerides (odds ratio: 1.05, 95 per cent CI: 1.02–1.12), total cholesterol (odds ratio: 1.12, 95 per cent CI: 1.05–1.26), and hypertension (odds ratio: 3.33, 95 per cent CI: 2.90–4.22) are significantly associated with residual dizziness.
This finding is also consistent with a cross-sectional study from Germany, which reported that hypertension and hyperlipidaemia were independently associated with residual dizziness in BPPV patients.Reference von Brevern, Radtke, Lezius, Feldmann, Ziese and Lempert2, Reference Chen, You, Wang, Wang and Dai29 The reason for this lies in the anatomical positioning of the SCC, which is at the lowest point in the vestibular apparatus when a person is standing.Reference Korres, Balatsouras, Kaberos, Economou, Kandiloros and Ferekidis18, Reference Chen, Zhang and Yang30 Von Brevern et al. discovered that BPPV predominantly affects the right labyrinth, likely due to the common habit among most patients of sleeping on their right side.Reference von Brevern, Radtke, Lezius, Feldmann, Ziese and Lempert2, Reference Korres, Balatsouras, Kaberos, Economou, Kandiloros and Ferekidis18 Theoretically, hypertension acts as a vascular risk factor, suggesting that ischemia might be a common predisposing factor for BPPV. However, our study did not identify any association between BPPV and other recognised vascular risk factors, including smoking and alcohol consumption (p > 0.05).Reference Ke, Ma, Jing, Diao and Yu17
BPPV patients exhibit higher total cholesterol levels, which have been identified as a risk factor for the occurrence of BPPV. The relationship between total cholesterol levels and BPPV has not been thoroughly explored in previous research. Elevated total cholesterol levels or hyperlipidaemia can cause vascular damage in the inner ear, potentially leading to BPPV.Reference Chen, Zhao, Yue and Zhang31 Additionally, a recent study discovered an association between the three rs2074880 genotypes of the CACNA1A (Calcium Voltage-Gated Channel Subunit Alpha1 A) gene and elevated cholesterol levels in patients with BPPV.Reference Dhiman and Joshi9, Reference Pan, Qi, Wang, Chong, Li and Chen32
Our study results also revealed the mediating role of total cholesterol levels in the relationship between sleep disorders and residual dizziness in BPPV patients. This finding highlights the importance of total cholesterol levels as a crucial intermediary factor. Elevated cholesterol levels, which are often a consequence of sleep disorders, can cause vascular damage in the inner ear, thus exacerbating dizziness symptoms. This mediating effect of total cholesterol levels suggests that managing cholesterol may help mitigate the effect of sleep disorders on residual dizziness.Reference Futami and Miwa33, Reference Ismail, Kabil and Abdel-Hamid34 For example, interventions aimed at reducing cholesterol levels could potentially disrupt the pathway linking sleep disturbances to dizziness, thereby improving patient outcomes.Reference Dhiman and Joshi9, Reference Alashram35, Reference Evans, Frost, Wood and Herdman36 Such evidence underscores the need for comprehensive treatment approaches that address both sleep quality and lipid management in BPPV patients to effectively reduce residual dizziness.Reference Çakır, Sahin, Gedik-Soyuyuce, Gence, Sertdemir and Korkut37–Reference Feng, Peng and Tao41
Several limitations of this study should be noted: (1) the sample size was relatively small, necessitating further validation and support from future research; (2) all the BPPV patients included were from a single location, which could restrict the generalisability of our findings; and (3) the retrospective analysis period of this study was relatively short. Future research should utilise large-scale prospective cohort studies to further elucidate the risk factors for residual dizziness in BPPV patients and the interactions between these factors.Reference Yang and Xiang42–Reference Chen, Zhu, You, Zhang and Dai45
• Benign paroxysmal positional vertigo is a common vestibular disorder, often treated with repositioning manoeuvres, but residual dizziness persists in some patients
• This study identifies sleep disorders, hypertension, medication treatment, and lipid levels as risk factors for residual dizziness
• This study is the first to show that total cholesterol mediates 9.1 per cent of the effect of sleep disorders on residual dizziness
• Managing both sleep disorders and lipid levels may help reduce residual dizziness in benign paroxysmal positional vertigo patients
Conclusion
Our findings indicate that sleep disorders, medication treatment, hypertension, triglycerides, and total cholesterol are significant risk factors for residual dizziness. Additionally, our study revealed a notable mediating effect (9.1 per cent) of total cholesterol blood concentration on the relationship between sleep disorders and residual dizziness. These insights underscore the importance of addressing lipid levels and sleep disorders in the management of residual dizziness in BPPV patients. Implementing targeted interventions for these factors could significantly improve patient outcomes and enhance the quality of care for those suffering from BPPV-related dizziness.
Supplementary material
The supplementary material for this article can be found at https://doi.org/10.1017/S0022215124001798.
Data availability statement
The datasets used and analysed during the current study are available from the corresponding author on reasonable request.
Availability of data and material
All data are included in the article and are available from the corresponding author.
Acknowledgements
This project was supported by Medical Science Research Project of Hebei Provincial Health Commission (20241029). Subject name: Exploring the driving factors of residual dizziness after successful reduction of otolithiasis.
Author contribution
The author, Guanyu Wang, contributed to all work of this study, including but not limited to design, data collection, analysis, and interpretation, drafting and revision of the article. The views expressed in this publication are those of the author.
Conflicts of interest
The author declares no conflict of interest.
