[version 1; peer review: 2 approved with reservations]
No competing interests were disclosed.
The gallbladder plays an essential role in lipid homeostasis through bile storage and regulated release. Gallstone disease is frequently associated with dyslipidemia, and cholecystectomy is one of the most common abdominal surgeries worldwide. However, its influence on serum lipid metabolism remains incompletely understood.
To evaluate changes in serum lipid profiles six months after cholecystectomy and assess whether the procedure contributes to improvement of dyslipidemia.
A prospective cohort study was conducted on 40 adult patients undergoing laparoscopic cholecystectomy for symptomatic gallstone disease between August 2024 and March 2025. Fasting lipid profiles—including LDL-cholesterol, HDL-cholesterol, triglycerides, total cholesterol, and VLDL—were measured preoperatively and at 6-month follow-up. The Atherogenic Index of Plasma (AIP) and total cholesterol/HDL ratio were calculated. Statistical analysis was performed using paired tests with significance set at p < 0.05.
Significant reductions were observed in total cholesterol (206.0 ± 37.1 to 194.8 ± 33.7 mg/dL, p = 0.003), LDL-cholesterol (128.7 ± 34.3 to 122.9 ± 31.6 mg/dL, p = 0.002), VLDL (25.2 ± 7.7 to 23.6 ± 7.8 mg/dL, p = 0.031), and the total cholesterol/HDL ratio (p = 0.004). HDL and triglyceride levels showed no significant change. AIP remained stable. Improvements were statistically significant but modest in magnitude.
Cholecystectomy was associated with small but significant reductions in total cholesterol and LDL-cholesterol six months postoperatively. Although the procedure is not a treatment for dyslipidemia, these findings suggest no adverse impact on lipid metabolism, and possibly a slight beneficial effect.
The gallbladder plays an essential role in the digestion and absorption of lipids by concentrating and storing hepatic bile, which is crucial for lipid homeostasis.
The absorption of cholesterol is primarily facilitated by the action of bile salts and phospholipids. An imbalance, such as an excess of cholesterol or a deficiency in bile salts or phospholipids, can lead to the crystallization of cholesterol and the formation of gallstones.
The
An earlier version of this work was posted online as a preprint.
This prospective, single-arm, before-after study was conducted on 40 adult patients with symptomatic gallstone disease who underwent laparoscopic cholecystectomy. Patients were recruited from the General Surgery department at Cairo University Hospital between August 2022 and March 2023. The study was designed to evaluate the impact of cholecystectomy on lipid profiles by comparing preoperative measurements with those taken at a 6-month postoperative follow-up.
The criteria for patient selection are summarized in
| Inclusion criteria | Exclusion criteria |
|---|---|
| Aged 18–65 years, with symptomatic gallbladder disease (e.g., recurrent biliary colic, nausea, right upper quadrant pain) | Acute cholecystitis at the time of evaluation (e.g., positive Murphy’s sign, fever, palpable RUQ mass, persistent severe pain > 48 hours, leukocytosis) |
| Documented gallstones on ultrasound (or radiologic signs of gallbladder inflammation) | Pregnancy or lactation |
| Able and willing to participate in the study and comply with follow-up requirements | On lipid-lowering medications or on a restrictive diet (e.g., vegetarian) known to affect lipid levels |
| Provided informed consent for surgery and study participation | Known metabolic disorders or comorbid conditions affecting lipid metabolism (e.g., untreated hypothyroidism) |
| History of hepatobiliary malignancy or other severe systemic illness | |
| Psychologically unable to consent or participate in long-term follow-up | |
| Refusal to undergo cholecystectomy |
The study was approved by the Cairo University Faculty of Medicine Research Ethics Committee (Approval No. MS-213-2022). All procedures were conducted in accordance with institutional guidelines and the Declaration of Helsinki. Written informed consent was obtained from each participant. Patient privacy was protected; all data were kept confidential and no personal identifiers are revealed in this report.
All patients underwent a thorough preoperative evaluation, including documentation of baseline demographic data (age, sex, weight, body mass index [BMI]) and clinical history. A fasting blood sample (>12 hours) was obtained at least one day before surgery to measure the baseline lipid profile.
Patients were followed up in the outpatient clinic, and at approximately 6 months postoperatively, a follow-up fasting lipid profile was obtained using the same methods as the preoperative testing. The 6-month interval was chosen to allow for the stabilization of any transient postoperative changes and to assess intermediate-term effects. All 40 patients returned for the 6-month blood test, representing a 100% follow-up rate. Patients were advised to maintain their usual diet and lifestyle during the follow-up period, and none initiated lipid-lowering therapy.
Serum triglycerides and total cholesterol were measured using standard enzymatic colorimetric assays. High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured using direct homogeneous enzymatic methods.
The
Data were analyzed using IBM SPSS Statistics version 25.0 (Armonk, NY: IBM Corp). Continuous variables were tested for normality using the Kolmogorov-Smirnov test. Normally distributed data are presented as mean ± standard deviation (SD), while non-normally distributed data are presented as median and interquartile range (IQR). Categorical variables are summarized as number (percentage). For paired comparisons of pre- and postoperative measurements, the paired Student’s t-test was used for parametric data, and the Wilcoxon signed-rank test was used for non-parametric data. The McNemar test was used to compare paired categorical data (e.g., the proportion of patients with abnormal values before vs. after surgery). A two-tailed p-value < 0.05 was considered statistically significant. No formal sample size calculation was performed prior to the study, which is a limitation. A post-hoc power analysis was planned to evaluate whether the sample of 40 patients was sufficient to detect clinically meaningful changes in lipids.
The study included 40 patients, of whom 30 (75%) were female. The mean age was 42.1 ± 8.9 years, and the mean Body Mass Index (BMI) was 30.2 ± 2.9 kg/m
2, indicating that the study population was, on average, overweight. The basic demographic characteristics of the patients are summarized in
| Parameter | Value |
|---|---|
| Gender | Male: 10 (25%); Female: 30 (75%) |
| Age (years) | Mean ± SD: 42.1 ± 8.9; Median [IQR]: 42.5 [36–48.5] |
| Weight (kg) | Mean ± SD: 81.9 ± 8.7; Median [IQR]: 82 [78–87.5] |
| BMI (kg/m 2) | Mean ± SD: 30.2 ± 2.9; Median [IQR]: 29.9 [28.4–32.1] |
Preoperatively, a high proportion of patients exhibited dyslipidemia based on the Adult Treatment Panel III (ATP III) criteria. As shown in
| Lipid parameter | No. (%) of patients with abnormal level |
|---|---|
| Total cholesterol (≥200 mg/dL) | 25 (62.5%) |
| LDL (≥100 mg/dL) | 34 (85%) |
| HDL (female, <50 mg/dL) | 16/30 (53.3%) |
| HDL (male, <40 mg/dL) | 1/10 (10%) |
| Triglycerides (≥150 mg/dL) | 16 (40%) |
| VLDL (>30 mg/dL, estimated) | 11 (27.5%) |
| Total cholesterol/HDL ratio > 5 | 16 (40%) |
As summarized in
| Parameter | Preoperative | Postoperative | P-value |
|---|---|---|---|
|
|
46.4 ± 6.6 | 46.2 ± 6.2 | 0.515 |
|
|
128.7 ± 34.3 | 122.9 ± 31.6 | 0.002 |
|
|
206.0 ± 37.1 | 194.8 ± 33.7 | 0.003 |
|
|
134 [106.75–162] | 130.5 [107–164.25] | 0.381 |
|
|
25.2 ± 7.7 | 23.6 ± 7.8 | 0.031 |
|
|
4.60 ± 1.29 | 4.35 ± 1.17 | 0.004 |
|
|
0.45 ± 0.15 | 0.455 ± 0.15 | 0.216 |
Values are presented as mean ± SD or median [IQR]. P-values were calculated using the paired Student’s t-test for normally distributed data and the Wilcoxon signed-rank test for non-normally distributed data.
In contrast, there were no statistically significant changes in mean HDL cholesterol levels (46.4 ± 6.6 vs. 46.2 ± 6.2 mg/dL; p = 0.515) or median triglyceride levels (134 vs. 130.5 mg/dL; p = 0.381). The Atherogenic Index of Plasma (AIP) also remained essentially unchanged (p = 0.216).
Despite the significant improvements in mean lipid levels, the proportion of patients with dyslipidemia did not change substantially after surgery. As shown in
| Lipid parameter | Preoperative, n (%) | Postoperative, n (%) | P-value |
|---|---|---|---|
| High Total Cholesterol | 25 (62.5%) | 19 (47.5%) | 0.07 |
| High LDL | 34 (85%) | 34 (85%) | 1.00 |
| Low HDL | 17 (42.5%) | 17 (42.5%) | 1.00 |
| High Triglycerides | 16 (40%) | 15 (37.5%) | 1.00 |
P-values were calculated using the McNemar test.
There were significant postoperative decreases in the liver enzymes alkaline phosphatase (ALP) (mean 87.8 → 73.3 IU/L; p = 0.005) and gamma-glutamyl transferase (GGT) (mean 46.3 → 38.1 IU/L; p = 0.001). The total leukocyte count (TLC) also showed a significant reduction (mean 8.43 → 7.40 ×10 9/L; p = 0.02). Other laboratory parameters, including hemoglobin, AST, ALT, creatinine, and INR, did not show significant changes.
In this prospective, single-arm, before-after study of 40 patients with symptomatic gallstone disease, we observed that cholecystectomy was associated with a modest but statistically significant improvement in serum lipid profile over a 6-month follow-up. Specifically, there were significant reductions in mean LDL cholesterol, total cholesterol, and VLDL cholesterol, whereas triglyceride and HDL levels did not change significantly. These findings suggest a potential metabolic benefit of gallbladder removal in terms of cholesterol reduction, but also highlight that the effect size is modest. For example, the observed ~5.5% reduction in total cholesterol is substantially less than what is typically achieved with pharmacological therapy or intensive lifestyle modifications for dyslipidemia. For context, statins can lower LDL cholesterol by 20-55%, which translates to a significant reduction in all-cause mortality and a 20-25% reduction in major cardiovascular events.
Our results are generally consistent with several recent studies that have reported improvements in lipid profiles after cholecystectomy. For instance, Singh et al. (2024) found significant postoperative decreases in total cholesterol, LDL, and triglycerides, and an increase in HDL at 1 month, in a larger cohort of 72 patients.
On the other hand, there are studies with conflicting results. Farrugia et al. (2024), who conducted a rigorous case-control study with a 1-year follow-up, reported no significant differences in lipid profiles after cholecystectomy, but a significant increase in triglycerides.
From a clinical perspective, our findings do not support the idea of cholecystectomy as a treatment for dyslipidemia per se. The improvements in LDL and total cholesterol, while statistically significant, were modest and may not meet thresholds for clinically meaningful risk reduction. No patient in our study achieved a complete normalization of their lipid profile on the basis of surgery if they were significantly dyslipidemic beforehand. Therefore, cholecystectomy should not be viewed as a therapeutic intervention for dyslipidemia. Rather, for patients requiring cholecystectomy for symptomatic gallstones, there might be a side benefit of slight lipid improvement or at least no worsening of lipid profile on average. This could be a useful point in patient counseling—for instance, patients often ask if gallbladder removal will affect their weight or cholesterol; we can inform them that on average their cholesterol might actually decline a bit.
An earlier version of this work was posted online as a preprint.
Despite these insights, our study has several limitations. First, the sample size of 40 patients is relatively small, which may limit the statistical power and generalizability of the results. Second, we did not include a control group of patients with gallstones who did not undergo surgery, which makes it difficult to distinguish the effects of surgery from the natural course of the disease or other secular changes. Third, the follow-up period of 6 months is relatively short and does not allow for an assessment of the long-term effects of cholecystectomy. Finally, we did not collect detailed data on dietary habits, physical activity, or other lifestyle factors post-surgery; as such, these factors could influence lipid levels independently of the surgery and were not accounted for in our analysis. These limitations should be considered when interpreting our findings, and they highlight the need for larger, controlled studies with longer follow-up and comprehensive lifestyle data to fully elucidate the impact of cholecystectomy on lipid metabolism.
In this prospective, single-arm, before-after study, cholecystectomy was found to be associated with statistically significant reductions in mean total cholesterol and LDL levels at 6 months postoperatively, without a notable impact on triglycerides or HDL. This suggests a modest, but favorable, short-term effect on the lipid profile in patients with symptomatic gallstone disease. However, the magnitude of this improvement was small and did not translate into a significant reduction in the proportion of patients with dyslipidemia. Cholecystectomy should not be considered a treatment for dyslipidemia, but patients can be counseled that their cholesterol may improve slightly after the surgery. Larger, controlled studies with longer follow-up are required to confirm these findings and determine their clinical significance for cardiovascular risk reduction.
Zenodo:
This project contains the following extended data:
Data are available under the terms of the
First of all, this study addresses an interesting and clinically relevant question regarding the metabolic consequences of cholecystectomy, particularly its potential influence on lipid profiles. The manuscript is generally well-structured, and the authors present their findings in a clear and concise manner. However, several important aspects need to be considered to strengthen the scientific rigor and interpretability of the results.
One of the main concerns lies in the study design, which is a single-arm, before–after approach. While this design allows for preliminary observations, it inherently limits causal interpretation. Without a control group of patients with gallstone disease who did not undergo surgery, it is difficult to determine whether the observed changes in lipid profiles are truly attributable to cholecystectomy or simply reflect natural variation over time. Factors such as regression to the mean or perioperative physiological changes may have contributed to the modest improvements reported.
Another critical limitation is the lack of control over confounding variables, particularly diet, physical activity, and weight changes. The manuscript mentions that patients were advised to maintain their usual lifestyle, but no objective data were collected to confirm adherence. This is important because postoperative dietary modification, especially reduced fat intake is very common after cholecystectomy and could independently explain the reduction in total cholesterol and LDL levels. Similarly, even small changes in body weight or BMI can significantly affect lipid metabolism, yet these variables were not reassessed at follow-up.
In addition, although the study reports statistically significant reductions in total cholesterol and LDL, the clinical relevance of these changes appears limited. The decrease in LDL (~6 mg/dL) and total cholesterol (~11 mg/dL) is relatively small and unlikely to translate into meaningful cardiovascular risk reduction, especially when compared to established interventions such as statins or structured lifestyle modification. The manuscript does acknowledge this to some extent, but the discussion could be more cautious in framing these findings, emphasizing the absence of harm rather than suggesting a beneficial metabolic effect.
The sample size (n=40) is another limitation. While acceptable for exploratory analysis, it reduces statistical power and generalizability. The absence of a priori sample size calculation further weakens the methodological robustness, even though this was transparently acknowledged by the authors.
From a reporting perspective, the manuscript would benefit from additional clarity in the Methods section, particularly regarding:
Whether any monitoring of dietary intake or physical activity was attempted Whether BMI or weight was reassessed postoperatively The exact formula used for calculating Atherogenic Index of Plasma (AIP)
Moreover, the inclusion of visual data representation (e.g., paired plots showing individual patient changes) would significantly improve the interpretability of the results and help readers better appreciate the variability and magnitude of change across participants.
Finally, while the discussion provides a reasonable mechanistic hypothesis involving bile acid metabolism, it remains largely speculative and not directly supported by measured biomarkers (e.g., bile acid levels or metabolic intermediates). Integrating more mechanistic or biochemical evidence would strengthen the translational value of the study.
In summary, this study provides useful preliminary insights suggesting that cholecystectomy does not adversely affect lipid profiles and may be associated with modest improvements. However, due to methodological limitations particularly the lack of a control group and unmeasured confounders the findings should be interpreted with caution. Future studies with larger sample sizes, controlled designs, and more comprehensive metabolic profiling are needed to confirm these observations and clarify their clinical significance.
Revise the title to make it more descriptive; avoid using the word “Impact” Include a more in-depth discussion of confounding factors Include (if available) data on changes in BMI and lifestyle Emphasize the difference between statistical and clinical significance Add a graph to clarify the data distribution Some references should be updated with recent studies that have had a significant impact
Major Revision
Is the work clearly and accurately presented and does it cite the current literature?
Partly
If applicable, is the statistical analysis and its interpretation appropriate?
Yes
Are all the source data underlying the results available to ensure full reproducibility?
Partly
Is the study design appropriate and is the work technically sound?
No
Are the conclusions drawn adequately supported by the results?
Partly
Are sufficient details of methods and analysis provided to allow replication by others?
Partly
Reviewer Expertise:
Clinical Nutrition, Obesity and metabolic disease and Functional Food
We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however we have significant reservations, as outlined above.
We thank the reviewers for their detailed and constructive evaluation. There is substantial overlap with the points raised by Reviewer 1, and where this is the case we have referred to our earlier responses to avoid repetition. We address each new or distinct point below.
Single-arm before-after design and causal interpretation
We agree, and refer the reviewers to our response to Reviewer 1, Major Suggestion 1. As outlined there, an observational control group of unoperated symptomatic patients was not feasible for ethical reasons, and we have substantially rewritten the Discussion and Limitations to make clear that causal attribution is not possible from this design.
Confounding: diet, physical activity, weight
We thank the reviewers and refer to our response to Reviewer 1, Major Suggestion 2. In brief: dietary intake and physical activity were not formally measured; BMI was recorded at baseline only. We have added these as explicit limitations and have noted in the Discussion that any of these factors could have contributed to the observed changes independently of the surgery itself. We have also added the clinical observation that, in our experience, the period of voluntary dietary fat restriction following cholecystectomy is typically limited to the first 7–10 postoperative days.
Statistical vs clinical significance
We agree completely; this overlaps with Reviewer 1's Major Suggestion 3. The Abstract, Discussion, and Conclusions have been rewritten so that the primary clinical message is the absence of an adverse effect on lipid metabolism. Language suggesting a clinically meaningful benefit has been removed.
Sample size and power
We acknowledge that the sample of 40 patients limits statistical power, particularly for secondary outcomes (HDL, triglycerides, AIP) for which we observed no significant change. As stated in the Methods, no a priori sample size calculation was performed; the cohort was assembled from consecutive eligible patients within the recruitment window. We have strengthened the Limitations section to reflect this and have explicitly framed the study as exploratory and hypothesis-generating, with results to be confirmed in larger, controlled cohorts.
Reporting clarity (diet, BMI, AIP formula)
All three points have been addressed in the revised Methods section:
Mechanistic discussion (bile acids)
We agree. We did not measure circulating or faecal bile acids, FGF19, 7α-hydroxy-4-cholesten-3-one (C4), or other intermediates of bile acid metabolism, so any mechanistic interpretation in our Discussion is necessarily speculative and based on the existing literature (notably Berr et al., 1989; Amigo et al., 2011). We have softened the language in the relevant Discussion paragraph to make explicit that this is a hypothesised mechanism not directly tested in the present study, and we have added a sentence recommending that future work incorporate direct measurement of bile acid kinetics
This prospective study addresses a clinically relevant question regarding the metabolic consequences of cholecystectomy. The manuscript is concise, and the authors have collected valuable preliminary data. However, several significant methodological limitations, most of which the authors transparently acknowledge, prevent definitive conclusions and temper the clinical implications of the findings. The study would be strengthened by a more rigorous discussion of confounding variables and a more cautious interpretation of the results.
1.The single-arm, before-after design is the primary limitation. As the authors correctly note in their discussion, the absence of a non-surgical control group with gallstone disease makes it impossible to attribute the observed lipid changes definitively to the cholecystectomy itself. The modest improvements observed could be explained by:
-Regression to the mean: Lipid levels measured during a symptomatic period may have been temporarily elevated due to pain, stress, or altered dietary intake.
-Post-operative lifestyle changes: Patients commonly modify their diet after surgery (e.g., reducing fat intake to avoid post-cholecystectomy symptoms), which could independently lower lipid levels.
2.The analysis does not account for factors that are known to significantly influence lipid profiles.
-Diet and Lifestyle: As mentioned above, post-operative dietary changes are a major potential confounder. Did the authors collect any data on dietary habits before and after surgery?
-Weight/BMI: Changes in weight can directly affect lipid levels. Was BMI or weight recorded at both time points? If patients lost weight post-operatively, this could explain the lipid changes.
The authors' acknowledgment of these limitations in their discussion is commendable. However, to strengthen the manuscript, the Methods section should specify whether any attempt was made to collect these data, and the Results should include a table comparing potential confounders (e.g., medication use, BMI) between the two time points.
3.The authors appropriately note that the observed changes are "modest" and that cholecystectomy is "not a treatment for dyslipidemia." The approximately 6 mg/dL reduction in LDL-cholesterol, while statistically significant (p = 0.002), is clinically negligible for an individual patient and far smaller than what is achievable with lifestyle modification or low-dose statin therapy. The most clinically reassuring finding is the absence of a harmful effect on lipid profiles, and the manuscript should frame this as the primary takeaway rather than suggesting a "beneficial effect."
1.The title "Impact of Cholecystectomy on Lipid Profile Levels..." is strong and causal. Consider a more neutral title like: "Changes in Lipid Profile Six Months After Cholecystectomy for Gallstone Disease: A Prospective Before-After Study. "
2.Specify the formula used for AIP.
3.The results are presented clearly. A simple figure (e.g., a paired scatter plot or a bar chart with before/after values and lines connecting individual patients) would visually enhance the manuscript and show the distribution of changes.
Is the work clearly and accurately presented and does it cite the current literature?
Yes
If applicable, is the statistical analysis and its interpretation appropriate?
Yes
Are all the source data underlying the results available to ensure full reproducibility?
Yes
Is the study design appropriate and is the work technically sound?
Partly
Are the conclusions drawn adequately supported by the results?
Partly
Are sufficient details of methods and analysis provided to allow replication by others?
Partly
Reviewer Expertise:
Gallstone diseases.
I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
We thank Dr. Hu for the careful reading and balanced critique. We agree that the methodological limitations need to be addressed transparently and that the framing of the findings should be more cautious.
Major Suggestion 1 — Single-arm, before-after design
We fully accept this limitation. The single-arm before-after design is indeed the primary methodological constraint of our study, and we have explicitly acknowledged this in the original manuscript. A non-surgical control group of patients with symptomatic gallstone disease was not feasible in our setting because, per current clinical guidelines, symptomatic cholelithiasis is an indication for surgery; deferring cholecystectomy in symptomatic patients to create an observational control group would have raised ethical concerns regarding withholding standard care.
With respect to regression to the mean, we have added explicit acknowledgement of this possibility in the revised Discussion. We note, however, that lipid profiles in our cohort were drawn at a non-acute outpatient visit at least one day before surgery — not during an acute symptomatic episode — which partially (though not completely) mitigates this concern.
With respect to post-operative dietary modification: based on our clinical experience, the dietary adjustment that follows cholecystectomy is typically transient and limited to roughly the first 7–10 postoperative days, during which patients tend to avoid fatty foods. Beyond this early recovery phase, the gallbladder removed at surgery was already a chronically diseased, contracted, and largely non-functioning organ, so most patients return to their habitual diet without sustained restriction. Nonetheless, we recognise that we did not formally measure dietary intake, and we have added this explicitly to the limitations.
Major Suggestion 2 — Confounding variables (diet, BMI, weight)
We thank the reviewer for this important point. We acknowledge that we did not systematically collect dietary intake records or repeat BMI measurements at the 6-month follow-up visit. The original protocol focused on lipid endpoints, and BMI was recorded only at baseline. Cholecystectomy is not a weight-reduction procedure, and in our routine clinical follow-up significant weight change at 6 months is uncommon; however, we accept that without measured data we cannot exclude small weight or BMI shifts as contributors to the observed lipid changes.
Regarding diet, as noted above, post-cholecystectomy dietary restriction in our population is typically short-lived (≈7–10 days) and we advised all patients to maintain their usual diet during the 6-month follow-up. We did not, however, capture this with food-frequency questionnaires or formal dietary recall, and we have added this as an explicit limitation.
Concomitant medications were screened at recruitment via the inclusion criteria — patients on lipid-lowering medication were excluded — and no patient initiated lipid-lowering therapy during follow-up, as already stated in the Methods.
Major Suggestion 3 — Reframe "beneficial effect" as "absence of harm"
We agree fully. We have rewritten the Conclusions, Abstract, and the closing of the Discussion to make clear that the principal clinically relevant message is the absence of a harmful effect of cholecystectomy on lipid metabolism at 6 months. The wording suggesting a possible "beneficial effect" has been removed or qualified, and we no longer present the modest LDL and total cholesterol reductions as clinically meaningful in isolation.
Minor Suggestion 1 — Title
We accept this suggestion. The revised title is:
This phrasing avoids the causal connotation of "Impact" and more accurately reflects the observational nature of the design.
Minor Suggestion 2 — AIP formula
We have added the formula to the Methods. The Atherogenic Index of Plasma was calculated according to Dobiášová and Frohlich (2001) as:
with both triglycerides and HDL-cholesterol expressed in mmol/L.