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Association between elevated serum total cholesterol and increased risk of post-induction hypotension in elderly patients undergoing non-cardiac surgery: a retrospective cohort study

Lipids in Health and Disease volume 24, Article number: 338 (2025) Cite this article

Abstract

Background

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Post-induction hypotension (PIH) is a frequent complication during general anesthesia and is linked to adverse outcomes. Abnormalities in serum total cholesterol (TC) have been associated with blood pressure dysregulation. This study investigated the relationship between preoperative serum TC levels and the risk of PIH in elderly patients undergoing non-cardiac surgery.

Methods

We retrospectively reviewed 821 elderly patients who received general anesthesia for non-cardiac surgery at our hospital between January 2019 and December 2021. Patients were categorized into a high TC group (≥ 5.2 mmol/L) and a normal TC group (< 5.2 mmol/L). Propensity score matching (PSM) was performed to reduce baseline differences, and perioperative hemodynamic outcomes were compared.

Results

PIH incidence was significantly higher in the high TC group than in the normal TC group (50.6% vs. 27.3%, p = 0.003). After PSM (n = 144 per group), the unadjusted risk of PIH was 1.74 times higher in the high TC group (95% confidence intervals [CI]: 1.24–2.45). Following adjustment for residual confounders, the increased risk persisted (adjusted risk ratio: 1.58; 95% CI: 1.12–2.23). Patients with high TC also showed greater reductions in blood pressure before (32% vs. 26%, p = 0.009) and after intubation (23% vs. 17%, p = 0.011).

Conclusions

Elevated preoperative serum TC is independently associated with a higher risk of PIH in elderly patients undergoing non-cardiac surgery. These results suggest that cholesterol metabolism contributes to perioperative hemodynamic instability and underscores the importance of including lipid status in preoperative risk assessment and anesthetic planning.

Background

Intraoperative hypotension is a major contributor to postoperative complications, particularly affecting critical organs such as the brain, heart, andkidneys [1, 2]. One of its most frequent forms is post-induction hypotension (PIH), which disproportionately impacts elderly patients. Owing to frailty, comorbid conditions, and reduced physiological reserves, older individuals are especially vulnerable to hypotensive episodes during anesthesia. Notably, nearly one-third of intraoperative hypotension cases arise between anesthetic induction and the start of surgery [3]. During this period, hypotension is primarily related to baseline hemodynamic status, anesthetic induction, and patient-specific factors, rather than surgical influences such as incision or blood loss [4]. Thus, PIH is a critical focus in the study of intraoperative hypotension. Reported risk factors for PIH include advanced age [4,5,6], the choice of induction agents [7], blood volume status [8], and brachial-ankle pulse wave velocity [9].

Total cholesterol (TC) is a well-recognized risk factor for cardiovascular disease. In a cohort of 3,090 elderly individuals, elevated TC levels were linked to increased all-cause mortality [10]. Similarly, a meta-analysis examining cholesterol and cardiovascular mortality confirmed a linear association between higher serum cholesterol and cardiovascular disease mortality [11]. Despite these findings, no studies to date have specifically investigated the relationship between TC and PIH in elderly patients.

The aim of this study was to evaluate the association between TC levels and the occurrence of PIH in elderly patients undergoing non-cardiac surgery, with the broader goal of informing strategies to prevent PIH, reduce related complications, and improve perioperative anesthetic management.

Methods

Study design and participants

This retrospective cohort study included elderly patients who underwent elective non-cardiac surgery at our hospital between January 2019 and December 2021. The study was approved by the Ethics Committee of QingPu Hospital Affiliated to Fudan University (IRB No. 2021-32, Chairperson: Bing Zhu; approval date: December 22, 2021) and registered with the Chinese Clinical Trial Registry. Informed consent was waived because of the retrospective nature of data collection.

The inclusion criteria were as follows: age 65–89 years; elective non-cardiac surgery; general anesthesia induced primarily with opioids (fentanyl or sufentanil) and propofol; and surgery lasting more than 30 min. Exclusion criteria included severe cardiopulmonary dysfunction or use of combined anesthesia techniques (e.g., spinal anesthesia or nerve block in addition to general anesthesia).

All anesthesia procedures followed standard clinical practice. Intravenous induction was typically administered in the following sequence: (midazolam) → opioid → propofol (and/or etomidate) → neuromuscular blocking agent. The induction rate, fluid management (timing and volume), and other intraoperative interventions were determined by the attending anesthesiologist.

Outcomes

Clinical data were retrospectively extracted from electronic medical records. Blood pressure was monitored non-invasively at four time points: T0 (before anesthesia induction), T1 (after induction but before intubation), T2 (after intubation), and T3 (5 min after intubation). Opioid dosage during induction was recorded and converted to morphine milligram equivalents (MME).

Based on previous reports [12, 13], TC < 5.2 mmol/L was considered normal. Therefore, patients were categorized into a high TC group (TC ≥ 5.2 mmol/L) and a normal TC group (TC < 5.2 mmol/L).

The primary endpoint was PIH incidence at T1, defined as mean arterial pressure (MAP) < 60 mmHg or a ≥ 30% decrease from baseline (T0). Because no standardized definition of PIH exists, with over 140 variations described in the literature [14], we adopted thresholds commonly used in studies of elderly patients to ensure clinical relevance and comparability [8, 15]. The secondary endpoint was the percentage reduction in blood pressure at T1, T2, and T3 compared with baseline, calculated as: (MAPT0 − MAPTx)/MAPT0 × 100%, where MAPTx represents MAP at T1, T2, or T3.

Statistical analysis

Although retrospective, the study included a validation of sample size. After propensity score matching (PSM), the final calculated sample size was 72 cases, which met statistical power requirements (α = 0.05, power = 0.80) as confirmed by post hoc testing. Continuous variables were expressed as mean ± standard deviation and compared using two-sample t-tests. Non-normally distributed variables were reported as median (P25, P75) and analyzed with Wilcoxon rank-sum tests. Categorical data were analyzed using the chi-square test or Fisher’s exact test.

To address baseline imbalances between the high and normal TC groups, a directed acyclic graph (DAG) was constructed for covariate selection. Rectangular nodes represented variables, with arrows denoting causal relationships (e.g., Age → TC). Exposure and outcome variables were highlighted separately, while other nodes indicated covariates. PSM (1:1) was then applied using caliper matching (caliper = 0.15). A corrected Poisson regression model was used to assess the association between TC and PIH, with results expressed as relative risk (RR) and 95% confidence intervals (CI). Generalized estimating equations were applied to evaluate differences in blood pressure reduction at T1, T2, and T3. All analyses were performed in Statistical Package for the Social Sciences 29.0 (IBM), with statistical significance set at two-tailed p < 0.05.

Sensitivity analyses were conducted to test robustness. These included: (1) excluding patients with hypertension to minimize medication bias; (2) re-analyzing data with alternative PIH definitions (MAP decline >40% and MAP < 70 mmHg) [16]; and (3) including intermediate variables excluded from the DAG model in PSM.

Results

The final analysis included 821 patients (Fig. 1), with 523 (63.6%) in the normal TC group and 298 (36.4%) in the high TC group. Before PSM, significant differences were observed in most baseline characteristics between the two groups (Table S1). Using a DAG model (Figure S1), potential confounders were identified, including age, sex, height, weight, LDL, HDL, glucose, body mass index, baseline MAP, baseline heart rate, propofol dosage, ASA classification, use of etomidate, and opioid induction dosage. After PSM, these variables were well balanced, resulting in a matched cohort of 144 patients, with 72 patients in each group (Fig. 2; Table 1).

Fig. 1
figure 1

Flowchart of patient inclusion and exclusion

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Fig. 2
figure 2

Pyramid chart of predicted probabilities for the two groups before and after propensity score matching (PSM). (A) Before PSM, (B) After PSM

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Table 1 Comparison of baseline characteristics between two patient groups after propensity score matching
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PIH at T1

After PSM, PIH incidence at T1 was significantly higher in the high TC group compared with the normal TC group (65.28% vs. 37.50%, p < 0.001) (Table 1). RR estimates for PIH at T1 are summarized in Table 2. Among the 144 matched patients, the unadjusted RR of PIH in the high TC group was 1.741 (95% CI: 1.236–2.452) compared with the normal TC group. After adjustment for age and sex (Model 1), the RR was 1.765 (95% CI: 1.262–2.467). When further adjusting for residual differences after matching, including midazolam use (Model 2), the RR remained elevated at 1.582 (95% CI: 1.122–2.232) (Table 2).

Table 2 Adjusted relative risk (RR) of pregnancy-induced hypertension in the high total cholesterol group compared to the normal total cholesterol group
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Reduction in blood pressure

The differences in blood pressure reduction rates between the two groups at matched time points (T1, T2, and T3) are presented in Table 3. After adjusting for age, sex, midazolam use, and inhalation agents, significant differences were observed at T1 and T2, whereas no significant difference was found at T3.

Table 3 Percentage of reduction in blood pressure at T1, T2, and T3 compared to T0
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Sensitivity analysis

Excluding hypertension

For this analysis, the original dataset (excluding missing data) was used. After excluding patients with hypertension, baseline characteristics showed significant differences in age, sex, height, weight, LDL, HDL, and triglycerides (TG) between the normal TC and high TC groups (Table S2). Results of the sensitivity analysis are summarized in Table 4. The unadjusted RR of PIH in the high TC group was 1.43 (95% CI: 1.05–1.94) compared with the normal TC group. After adjustment for age and sex (Model 1), the RR was 1.40 (95% CI: 1.01–1.95). With further adjustments for height, weight, LDL, HDL, and TG (Model 2), the RR increased to 1.80 (95% CI: 1.13–2.87).

Table 4 Summary of sensitivity analysis and the relative risk models
Full size table

Outcome measure

The original dataset, excluding missing values, was used for this analysis. Based on propensity score–matched data, we also found a significant difference in PIH incidence when alternative outcome definitions were applied (MAP decline >40% or MAP < 70 mmHg), as reported in previous studies [5, 16]. As shown in Table 4, the unadjusted analysis indicated that patients in the high TC group had a 1.73-fold higher risk of PIH (95% CI: 1.14–2.63) compared with the normal TC group. After adjusting for age and sex (Model 1), the risk remained elevated (RR 1.72; 95% CI: 1.14–2.60). Further adjustment for residual variables, including HDL and midazolam use (Model 2), yielded an RR of 1.63 (95% CI: 1.07–2.48).

Mediating variable

In this analysis, the original dataset with missing values excluded was used. Mediating variables identified by the DAG model were incorporated into the PSM, yielding a total of 142 matched patients. Figure S2 shows the pyramid plot of predicted probabilities after matching, while Table S3 summarizes the characteristics of patients in the normal TC and high TC groups. As the unmatched population pyramid was already presented in Fig. 2A, Figure S2 exclusively depicts the matched cohort. As shown in Table 4, the unadjusted RR of PIH in the high TC group was 1.65 (95% CI: 1.06–2.58) compared with the normal TC group. After adjusting for age and sex (Model 1), the risk remained elevated (RR 1.64; 95% CI: 1.05–2.56). Further adjustment for residual variables, including MME (Model 2), yielded a similar risk estimate (RR 1.63; 95% CI: 1.04–2.55). These sensitivity analyses consistently demonstrated that patients with high TC had a higher risk of PIH compared with those in the normal TC group.

Discussion

Our findings demonstrated that the RR of PIH was 1.5–1.8 times higher in the high TC group compared with the normal TC group. This suggests that elevated preoperative cholesterol levels are associated with a greater likelihood of PIH in elderly surgical patients. However, this association does not confirm causality. Instead, cholesterol levels may serve as a potential marker for PIH risk. Further prospective studies are needed to clarify this relationship and assess its implications for preoperative lipid management.

Hypercholesterolemia has long been recognized as a metabolic disorder that promotes endothelial dysfunction and arterial atherosclerosis by impairing endothelium-dependent vasodilation [17, 18], primarily through reduced nitric oxide bioavailability and increased plasma viscosity [19]. These vascular changes result in stiffer, less compliant vessels that may be unable to adequately respond to the vasodilation triggered by general anesthetic agents [20, 21], thereby increasing susceptibility to PIH. In patients with hyperlipidemia, chronic low-grade inflammation and endothelial dysfunction can impair sympathetic nervous system responsiveness [22], attenuating compensatory mechanisms such as reflex tachycardia and peripheral vasoconstriction [23]. Hyperlipidemia is also frequently associated with diastolic dysfunction, particularly in elderly patients and those with hypertension, rendering cardiac output heavily preload-dependent [24]. During anesthesia induction, vasodilation sharply reduces preload, further lowering cardiac output and aggravating hypotension [25]. Furthermore, hyperlipidemia disrupts the vascular benefits of high shear stress, which normally promotes adaptive arterial dilation and remodeling [26]. These interrelated mechanisms, together with common comorbidities such as hypertension, diabetes, coronary artery disease, and obesity, may act synergistically to increase the risk of PIH [27]. Previous studies have highlighted arterial stiffness, measured by brachial-ankle pulse wave velocity, as a strong predictor of PIH, consistent with our findings. Evidence also suggests that lipid-lowering medications can influence blood pressure and benefit patients with hypertension and dyslipidemia [28], though it remains unclear whether statin therapy in patients with isolated hyperlipidemia prevents hypertension. Our study specifically examined the association between preoperative lipid levels and hypotension after anesthesia induction, with the reliability of the findings strengthened by a sensitivity analysis excluding patients with hypertension.

Our study observed that elevated TC levels may be linked to greater reductions in blood pressure. A previous retrospective cohort study reported that a MAP of ≤ 65 mmHg during non-cardiac surgery was associated with myocardial and renal injury, with the risk increasing when MAP ≤ 65 mmHg persisted for 13 min or longer, and even brief episodes of MAP ≤ 50 mmHg lasting as little as 1 min further exacerbated these effects [29]. These findings highlight that even short-term hypotension may cause cardiac and renal damage, underscoring the importance of monitoring elevated TC levels. In our analysis, we did not include preoperative use of lipid-lowering medications as a covariate, as the study focused on laboratory test results obtained before surgery. This aspect warrants further investigation in future research.

Following PSM, a significant difference in the concomitant use of midazolam between the two groups remained. A randomized controlled trial previously demonstrated that co-induction with propofol and midazolam reduced the required propofol dose and provided more stable hemodynamics compared with propofol alone [30]. Although co-induction was not systematically applied in our study, the concurrent use of midazolam may still have influenced PIH incidence. In our cohort, midazolam was more frequently administered in the normal TC group than in the high TC group, which could partially explain the observed difference. This imbalance was adjusted for in our statistical models. Importantly, including midazolam as a covariate did not materially change the association between TC and PIH, suggesting its clinical impact was limited. Furthermore, midazolam in our study was typically given inconsistently and at low premedication doses rather than in a standardized co-induction regimen, making its hemodynamic effect likely modest. Nevertheless, the possibility of residual confounding cannot be excluded, and prospective studies with standardized induction protocols are warranted to clarify whether midazolam exerts a meaningful effect.

Preoperative use of ACEI/ARB medications has also been reported as a risk factor for PIH [15, 25]. Similarly, previous studies have suggested that lipid-lowering agents such as statins may exert modest blood pressure–lowering effects and provide additional benefits in patients with hypertension and dyslipidemia [28]. However, these studies did not specifically investigate whether statin use in patients with isolated hypercholesterolemia could prevent hypertension. In addition, suboptimal adherence and inadequate dosing of lipid-lowering therapy are common in clinical practice [31], complicating interpretation. Considering the lack of strong evidence supporting ACEI/ARB or statins in preventing perioperative hypotension, we focused on preoperative laboratory values rather than medication histories. To further address potential confounding, we conducted a sensitivity analysis excluding patients with hypertension, which confirmed the robustness of our findings.

Limitations

This study has several limitations. First, as with all retrospective observational analyses, although we adjusted for the most relevant known confounders, the possibility of residual or unmeasured confounding cannot be excluded; therefore, the observed association between TC and PIH should not be interpreted as causal. Second, our study population consisted of elderly patients undergoing elective non-cardiac surgery without severe cardiopulmonary comorbidities. Consequently, the findings may not be generalizable to patients undergoing emergency procedures or to critically ill populations in whom baseline physiology, perioperative management, and the interaction between lipid levels and hemodynamic responses may differ substantially. Third, although the main induction agents were standardized to propofol and opioids (sufentanil and fentanyl), and adjustments were made for the concomitant use of etomidate and midazolam, variability in anesthesiologists’ practice patterns could not be fully controlled. Factors such as preoperative volume status, peri-induction fluid administration, and drug dosages were not standardized and may have influenced hemodynamic outcomes. These issues warrant further investigation in prospective studies. Finally, the impact of ACEI/ARB use, recognized as a potential confounder, requires further evaluation in future research.

Furthermore, we defined high TC as ≥ 5.2 mmol/L, corresponding to the upper limit of the reference range in our hospital laboratory. This threshold has also been applied in previous studies, including a prospective cohort investigating hyperlipidemia and postoperative delirium [12] and the Berlin Aging Study II examining hypercholesterolemia in older adults [13]. However, lipid metabolism is strongly influenced by age and sex [32]. For instance, elderly patients often exhibit altered lipid profiles due to age-related changes in hepatic metabolism, hormonal shifts, and comorbid conditions [33, 34], whereas women—particularly after menopause—tend to have higher TC levels compared with age-matched men [35]. These biological differences suggest that a single threshold may not be universally applicable across diverse populations. Although 5.2 mmol/L provides a pragmatic and standardized cutoff, its limitations should be recognized. Future prospective studies are needed to determine whether age- or sex-specific thresholds might improve risk stratification for PIH.

Conclusions

In conclusion, elevated preoperative TC levels were linked to a higher PIH incidence in elderly patients undergoing elective non-cardiac surgery. This association remained significant after adjustment for confounders, with sensitivity analyses reinforcing the robustness of the findings. While cholesterol levels may represent a useful marker for PIH risk stratification, causality cannot be inferred. Prospective studies are warranted to validate these results, elucidate underlying mechanisms, and identify potential preventive strategies.

Data availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

Not applicable.

Funding

This study was supported by Hospital level project of QingPu Branch of Zhongshan Hospital Affiliated to Fudan University [grant number: QY2021-05]; and Shanghai Jiao Tong University “Jiao Tong University Star” Program Medical and Industrial Cross Research Fund [grant number: YG2022QN068].

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Authors and Affiliations

  1. Department of Anesthesiology, QingPu Hospital Affiliated to Fudan University, No.1158 Park Road (E), 201700, Shanghai, China

    Yiying Yang & Hui Jiang

  2. Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 650, New Songjiang Road, Shanghai, 201620, China

    Chao Gong, Zhenyu Luo & Lianhua Chen

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  1. Yiying Yang
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  2. Chao Gong
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  3. Hui Jiang
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  4. Zhenyu Luo
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Contributions

Y.Y. contributed to data collection, data analyze and manuscript writing; Z.L. contributed to data collection; C.G. analyzed the data and contributed to the conception of study; L.C. contributed to project guidance; H.J. collected and analyzed the data.

Corresponding author

Correspondence to Chao Gong.

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Ethics approval and consent to participate

The study protocol was approved by the Research Ethics Committee and registered at Chinese Clinical Trial Registry. Ethical approval for this study (IRB Number: 2021-32) was provided by Ethics Committee of QingPu Branch of Zhongshan Hospital Affiliated to Fudan University (Chairperson: Bing Zhu), on 22 December 2021. Informed consent was waived due to the retrospective collection of data.

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The authors declare no competing interests.

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Yang, Y., Gong, C., Jiang, H. et al. Association between elevated serum total cholesterol and increased risk of post-induction hypotension in elderly patients undergoing non-cardiac surgery: a retrospective cohort study. Lipids Health Dis 24, 338 (2025). https://doi.org/10.1186/s12944-025-02758-5

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Keywords

Lipids in Health and Disease

ISSN: 1476-511X