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Article

Cardiovascular Risk Assessment in the Immediate Postoperative Period of Bariatric Surgery

by
Letícia de Oliveira Souza Bratti
1,2,
Ana Carolina Martins
1,
Bruno Fonseca Nunes
1,
Emerita Quintina de Andrade Moura
3,
Ana Carolina Rabello de Moraes
1,2 and
Fabíola Branco Filippin-Monteiro
1,2,*
1
Programa de Pós-Graduação em Farmácia, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, Florianópolis 88040900, Brazil
2
Departamento de Análises Clínicas, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, Florianópolis 88040900, Brazil
3
Laboratório de Análises Clínicas, Hospital Universitário, Universidade Federal de Santa Catarina, Florianópolis 88040900, Brazil
*
Author to whom correspondence should be addressed.
Obesities 2025, 5(1), 5; https://doi.org/10.3390/obesities5010005
Submission received: 20 December 2024 / Revised: 7 January 2025 / Accepted: 17 January 2025 / Published: 22 January 2025
Figure 1
<p>Fasting glucose (<b>A</b>), insulin (<b>B</b>), HDL cholesterol (<b>C</b>), non-HDL cholesterol, in subfigure C a red line was drawn to separate participants with HDL above and below 40 mg/dL (<b>D</b>), triglycerides (<b>E</b>), Castelli-I index (<b>F</b>), Castelli-II index (<b>G</b>), TG/HDL cholesterol (<b>H</b>) and non-HDL/HDL cholesterol (<b>I</b>) before, 1, 3, and 6 months after bariatric surgery. * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01; *** <span class="html-italic">p</span> &lt; 0.001; **** <span class="html-italic">p</span> &lt; 0.0001.</p> ">
Figure 2
<p>HDL cholesterol levels are above and below the reference value percentage. RV: reference value. * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01.</p> ">
Figure 3
<p>Results expressed in individual values and the median. (<b>A</b>) HDL particle size (nm); (<b>B</b>) individual analysis of HDL particle size; (<b>C</b>) PoI. Wilcoxon test was applied in (<b>A</b>,<b>B</b>), (<span class="html-italic">p</span> &gt; 0.05). Source: Prepared by the author.</p> ">
Figure 4
<p>Results expressed in individual values and the median. (<b>A</b>) LDL particle size (nm), (<b>B</b>) Atherogenicity Index of Plasma; (<b>C</b>) Castelli Index I; (<b>D</b>) Castelli Index II; Wilcoxon test. *** <span class="html-italic">p</span> &lt; 0.05. Source: Prepared by the author.</p> ">
Review Reports Versions Notes

Abstract

:
Objectives: Since obesity and overweight are strongly associated with cardiovascular diseases, we investigated cardiovascular events risk in individuals who lost weight through bariatric surgery. Methods: Serum levels of glucose, insulin, triacylglycerol, HDL cholesterol, non-HDLDL cholesterol, and lipoprotein ratios were assessed in patients with obesity before and after bariatric surgery, including a 6-month follow-up period. Results: Bariatric surgery significantly improved BMI, triglyceride levels, glucose, and insulin sensitivity. However, HDL cholesterol levels dropped sharply in the first month (p < 0.0001), coinciding with elevated atherogenic indices, indicating a transient increase in cardiovascular risk. By 6 months, indices improved significantly, HDL recovered, and LDL particle size increased, suggesting reduced atherogenic potential. Conclusions: Individuals undergoing bariatric surgery have a higher cardiovascular events risk in the immediate postoperative period. Health professionals should be aware of and monitor these patients closely.

1. Introduction

Obesity and overweight are characterized as abnormal or excessive fat accumulation that may compromise health. For adults, obesity is defined by a BMI (body mass index) ≥ 30 kg/m2 and overweight by a BMI ≥ 25 kg/m2. Elevated BMI is a major risk factor for noncommunicable diseases such as dyslipidemia, cardiovascular diseases, type 2 diabetes, musculoskeletal disorders, and some cancers. Furthermore, it is associated with an increased risk of cardiovascular mortality. Thus, obesity and overweight have become a global public health question and are linked to more deaths worldwide than being underweight. Some 2016 data estimate that 1.9 billion adults aged 18 years and older were overweight (39% of the world’s adult population), and of these, more than 650 million were obese (13%) [1,2].
Adipose tissue has been described as an active endocrine and immunological organ, which stores the largest body lipids amount, including triglycerides and free cholesterol. In obesity, excessive adipose tissue accumulation and adipocyte hypertrophy can promote pathogenic effects, resulting in abnormal circulating lipids levels [3]. About 60% of patients with severe obesity have some form of dyslipidemia [4]. In these cases, atherogenic dyslipidemia is characterized by increased triglyceride serum concentrations, low high-density lipoprotein (HDL)–cholesterol levels, and nearly normal low-density lipoproteins (LDL) cholesterol levels concomitantly with an increased proportion of small and dense LDL particles [5]. It is well established in the medical literature that low HDL cholesterol levels are an independent risk of coronary heart disease predictor and there is a strong inverse association between HDL cholesterol levels and coronary heart disease events incidence [6]. Osto et al. found abnormalities in HDL particles from individuals with obesity that could be compared to an HDL subpopulation profile of individuals with established cardiovascular disease [7].
Severe obesity treatment through pharmacological or lifestyle interventions, such as dietary re-education and physical exercise, is insufficient to induce sustained weight loss and metabolic conditions and comorbidities lasting remission. On the other hand, a pronounced and lasting weight loss associated with obesity metabolic condition improvement, including dyslipidemia, is possible with bariatric surgery [5,8]. Metabolic recovery after bariatric surgery is associated with a decrease in overall mortality, induced by a cardiovascular mortality reduction [9]. Follow-up studies of patients undergoing bariatric surgery have shown fasting and postprandial triglyceride levels marked reductions, HDL cholesterol levels increases, and atheroprotective changes in the LDL and HDL particle composition and function after the procedure [4,10].
For cardiovascular risk assessment, the use of indexes is widespread. Indexes are often more powerful predictors of coronary risk than other measures used separately. It is common to use the Castelli-I and -II risk indexes and the TG/HDL cholesterol ratio. Castelli-I risk index, also known as the cardiac risk ratio, can reflect the formation of the coronary plaques with a diagnostic value as good as total cholesterol determination [11,12], while the Castelli-II risk index is used as a good cardiovascular risk predictor [13]. Finally, the TG/HDL cholesterol ratio has been correlated with insulin resistance and acute myocardial infarction prediction [14,15]. Therefore, the objective of this study was to evaluate individuals undergoing bariatric surgery cardiovascular risk based on conventional lipid markers and risk indexes.

2. Materials and Methods

2.1. Participant Selection

Volunteers with obesity who underwent bariatric surgery by RYGB or SG from August 2014 to November 2015 and November 2018 to November 2019 at University Hospital Professor Polydoro Ernani de São Thiago (HU-UFSC), a tertiary university hospital in Florianopolis, South Brazil, were selected for this study. All patients complied with the criteria for bariatric surgery established by the National Institutes of Health (NIH) [16] (Table S1). The group included individuals with BMI ≥ 40 kg/m2 or BMI ≥ 35 kg/m2 with weight-related comorbidities. Participants were verbally briefed about this study and signed an informed consent document approved by the Ethics Committee of the State University of Santa Catarina. This study was registered under the n° 24279013.7.0000.0121.

2.2. Data Collection and Serum Obtainment

Information about gender, age, BMI, comorbidities, and drug use was obtained from the medical records of each patient. Fasting blood samples were collected before and one, three, and six months after surgery. Fasting was defined as 10 h or more since the last meal before blood collection. Serum was separated, aliquoted, and subsequently stored at −80 °C.

2.3. Serum Assays

Total cholesterol, triacylglycerol, HDL cholesterol, and glucose were measured using enzymatic methods (Dimension RXL Max, Siemens, Berlin, Germany). LDL cholesterol was calculated by the Friedewald equation, and serum insulin was measured by the immunochemiluminometric method (Advia Centaur XP, Siemens, Berlin, Germany).
The reference values used were based on the Adult Treatment Panel (ATP) III Guidelines [16,17]. Castelli-I and -II risk indexes were calculated with the formulas: total/HDL cholesterol and LDL/HDL cholesterol, respectively. In addition, we calculated the ratio of TG/HDL cholesterol and non-HDL cholesterol/HDL cholesterol.

2.4. Statistical Analysis

The Shapiro–Wilk test was used to evaluate the symmetry of variables, the Friedman test was used to evaluate differences between the entire follow-up, and the Wilcoxon test was used to assess paired changes before and after surgery. These three tests were used in ordinal variables analysis. To continue the data, the McNemar test was used to assess paired changes before and after surgery. Data were analyzed using Medcalc statistical software program, version 16.8.4 (Mariakerke, Belgium) and were illustrated using GraphPad Prism 5.0 (GraphPad Software, Inc., San Diego, CA, USA). A p-value ≤ 0.05 was considered to indicate statistical significance.

2.5. Determination of HDL Particle Size in Patients Undergoing Bariatric Surgery

To determine the particle size of HDL, low-density lipoproteins (VLDL, IDL, and LDL) were precipitated from serum samples using 1.5 mmol/L phosphotungstic acid and 54 mmol/L magnesium chloride, reagents included in the HDL-c determination kit. A 25 μL sample was mixed with 25 μL of precipitant, followed by centrifugation at 3000× g for 15 min to obtain a clear supernatant (CS) rich in HDL. The CS was then diluted with 0.9% (w/v) sodium chloride (NaCl) in a 1:4 ratio (CS–diluent). For the filtration step, aimed at removing impurities and precipitates, a 0.22 μm pore-size filter Ultrafree®-MC, 0.5 mL (MilliporeSigma, Burlington, MA, USA) was used, followed by centrifugation at 12,000× g for 4 min. Subsequently, the samples were analyzed using the dynamic light scattering (DLS) technique on the Zetasizer Nano instrument (Malvern Panalytical, Spectris, London, UK). Quartz cuvettes designed for small volumes were used for the readings. Final data were obtained as the average of three “runs” performed by the instrument, each comprising 10–30 measurements.

2.6. Atherogenic Indices

To determine atherogenic indices and calculate the LDL particle size in plasma samples, the following equations were used, based on the recommended scientific literature.
For the calculation of IC-I (1), the ratio of total cholesterol to HDL-c was employed, following the formula proposed by Castelli et al. [18]:
I C I = C T / H D L c
Additionally, IC-II (2) was obtained through the ratio of LDL-c to HDL-c, also using the formula by Castelli et al. [18]:
I C I I = L D L c / H D L c
The AIP (Atherogenic Index of Plasma) (3) was calculated using the equation formulated by Dobiášová and Frolich [19], considering the logarithm of the ratio between triglycerides and HDL-c as follows:
I A P = l o g T G H D L c
To determine LDL particle size (4), the equation proposed by Maruyama, Imamura, and Teramoto [20] was applied, which considers the relationship between triglycerides (TG) and HDL-c as follows:
L D L n m = 26.262 0.776 · T G H D L c

3. Results

3.1. Individual’s Characteristics

At the beginning of this study, eighty-two subjects with obesity underwent evaluation. The median age was 43 years, and 83% of participants comprised women. The median BMI in the preoperative period was 48 kg/m2 and, at the end of follow-up, six months later, decreased to 34 kg/m2 (p < 0.0001). Additional tracking data are shown in Table 1.

3.2. Lipidic and Glycemic Profile

In lipid profile evaluation, differences between follow-up times were observed for HDL cholesterol and triglycerides (p < 0.0001). For non-HDL cholesterol, no differences were observed (p = 0.0753). In addition, all indexes calculated showed a significant difference: p = 0.0037 for the Castelli-I index, p = 0.0014 for the Castelli-II index, p < 0.0001 for the TG/HDL cholesterol ratio and p = 0.0037 for the n-HDL/HDL cholesterol ratio. Data are shown in Table 1.
To analyze in which periods the differences were found, paired analyses were performed between the preoperative values and the three follow-up values. For non-HDL cholesterol, we did not find differences at any follow-up period. For triglycerides and fasting glucose, compared to the preoperative period, we found a significant decrease after three months (p = 0.0208 for triglycerides and p < 0.0001 for fasting glucose) and six months (p < 0.0001 both). For insulin, a decrease was observed in the first month (p = 0.0008) and continued to fall after three (p = 0.0003) and six months (p < 0.0001). In the HDL cholesterol analysis, a sharp drop was observed in the first month (p < 0.0001), a less significant drop in the third month (p = 0.0035), and no difference was observed in the sixth month. For the Castelli-I index and non-HDL/HDL cholesterol ratio, a significant increase was observed in the first month (p = 0.0243) and a significant decrease in the sixth month (p = 0.0387). For the Castelli-II index and TG/HDL cholesterol, only an increase was observed after six months (p = 0.0266 and p = 0.0002, respectively). The assessment of lipidic and glycemic markers is shown in Figure 1.
Since previous analyses were based on absolute values, we decided to analyze the HDL cholesterol values’ practical implications. Values were divided into two groups: below or above the reference value. Before the surgical procedure, only 35% of the participants had HDL cholesterol levels below the reference value, while, in the first postoperative month, 76% of the participants had HDL cholesterol levels below the reference value, followed by 47% in the third month and 29% in the sixth month. When these nominal variables were compared to each other, significant differences were found between preoperative vs. 1 month (p = 0.0352); 1 month vs. 3 months (p = 0.0129); 1 month vs. 6 months (p = 0.0013). These results are shown in Figure 2.

3.3. HDL Particle Size in Patients Undergoing Bariatric Surgery

During this study, serum samples from twenty-seven patients recruited at the University Hospital Professor Polydoro Ernani de São Thiago (HU-UFSC) who underwent bariatric surgery were analyzed.
Figure 3 illustrates the comparison of HDL particle size and polydispersity index (PdI) between the preoperative and postoperative periods (1 year). The overall analysis of HDL particle size (Figure 3A) revealed no statistically significant difference between the two periods (Wilcoxon test, p > 0.05). In the pre-bariatric period, particle size ranged from 10.34 to 14.85 nm, with a median of 12.25 nm, while in the post-bariatric period, the range was 9.95 to 14.34 nm, with a median of 12.08 nm. Individual analysis of particle size (Figure 3B) showed that most patients (n = 19) exhibited a decrease in HDL particle size, though this change was not statistically significant, while a smaller group (n = 8) demonstrated an increase. In addition to particle size, the polydispersity index (PdI) was analyzed (Figure 3C), revealing low dispersion overall, with values ranging from approximately 0.2 to 0.4. A few outlier points were observed but deemed valid due to the presence of a distinct peak within the expected HDL range and satisfactory internal quality control of the equipment.
LDL particle size, as shown in Figure 4A, significantly increased after bariatric surgery, with the median size rising from 25.2 nm preoperatively to 25.7 nm postoperatively (p < 0.05). Notably, all patients exhibited an increase in LDL particle size following the intervention. In addition to LDL size, atherogenic indices displayed significant improvements after surgery. The Atherogenic Index of Plasma (AIP) (Figure 4B) decreased from a median of 0.49 preoperatively to 0.19 postoperatively (p = 0.0002). Similarly, Castelli Index I (Figure 4C) dropped from 3.94 to 2.96 (p = 0.0006), and Castelli Index II (Figure 4D) showed a significant reduction, with values decreasing from 2.388 to 1.682 (p = 0.0003). Together, these results indicate a marked improvement in lipid profile and reduced atherogenic risk following bariatric surgery.

4. Discussion

Through the significant decrease in the glucose, insulin, and triglycerides levels, as well as Castelli-I and II indexes and TG/HDL cholesterol and non-HDL/HDL cholesterol ratios, the present study confirms the beneficial effects of bariatric surgery on lipidic and glycemic profile. However, we highlight the sharp decreased in HDL cholesterol levels in the first month after surgery.
Some previous studies have also shown a marked decrease in HDL cholesterol levels during the first weight loss phase with different weight loss strategies. This phenomenon occurs not only with bariatric procedures but also with nutritional weight loss, especially with fat restriction and with some weight management pharmacotherapies. In previous studies that reported this initial transient decline, after the first phase of weight loss, HDL levels gradually increased and reached levels of up to 47% above preoperative values 10 years after surgery [21,22,23,24,25,26]. Nonetheless, few have discussed in depth the lowering of HDL reasons and risks at weight loss onset.
In 1953, it was reported that HDL cholesterol levels were significantly lower in subjects with coronary artery disease compared to healthy controls [27]. Since then, the negative impact of low HDL and high LDL levels on cardiovascular health is well established. The Framingham Heart Study showed that myocardial infarct risk increases by approximately 25% for every 5 mg/dL decrease in serum HDL below median values. This risk is independent of the risk attributed to elevated levels of LDL [28,29]. Observational data such as these have led to the idea that HDL may have properties that protect against coronary heart disease and that intervention to increase HDL cholesterol would reduce the risk of coronary heart disease. Several preclinical studies have supported the hypothesis that HDL cholesterol is protective against atherosclerosis and, combined with epidemiological data, have strongly reinforced the HDL hypothesis, making HDL a target for new therapeutic approaches [30,31,32]. However, genetic evidence and randomized clinical trials over the last years indicated that HDL cholesterol concentrations do not seem to be a viable therapeutic path for cardiovascular prevention [33,34,35]. Despite this, it is important to emphasize that the value of HDL cholesterol as a predictor of cardiovascular risk remains largely uncontested. Many prospective studies in different populations have confirmed that HDL cholesterol is a strong, consistent, and independent predictor of cardiovascular events incidence of such as myocardial infarction and ischemic stroke since it reflects a high level of TG and atherogenic remnant lipoproteins [36,37].
In the present study, we identified a marked HDL cholesterol level decrease in the first postoperative month, which continued to a lesser extent in the third month and was no longer observed at the end of follow-up. The first statistical tests carried out evaluated the HDL cholesterol absolute values; therefore, to assess the practical implications of this decrease, we divided the participants into two groups: below and above the reference value (40 mg/dL). With this analysis, we observed that, in the first postoperative month, 76% of the participants had HDL cholesterol below the reference value, followed by 47% in the third month. These results confirm the increased cardiovascular events risk in the immediate bariatric surgery postoperative.
One of the explanations for the decrease in HDL cholesterol levels in obesity is due to the activity of cholesterol ester transfer protein (CETP). CETP mediates the transfer of TG from TG-rich particles to HDL and the transfer of esterified cholesterol from HDL to these particles. Since a TG molecule is significantly larger than a cholesterol ester molecule, replacing cholesterol esters with TG increases the size of HDL. Under circumstances where plasma TG levels are high, the transfer of cholesterol esters from HDL exceeds that of TG. This generates core lipid-depleted HDL particles with excess surface constituents and compromised structural stability. These resulting large particles are the preferred substrate for the hepatic lipase enzyme and are eliminated by the liver. Obesity also increases hepatic lipase activity [38,39]. Some studies reported a reduction in plasma CETP activity and hepatic lipase activity induced by weight loss after bariatric surgery, leading to a more favorable lipoprotein profile [40,41,42].
The usefulness of HDL cholesterol as an independent risk predictor is shown by its continued use in cardiovascular risk equations. The cardiovascular risk measures, based on calculations such as Castelli-I and -II risk indexes and TG/HDL cholesterol ratio, are very common. Still, recently, non-high-density lipoprotein (non-HDL) cholesterol has emerged as a new target for the prevention of cardiovascular events. The International Atherosclerosis Society and the Brazilian Cardiology society guidelines state that non-HDL cholesterol is relevant to the prevention and is a therapeutic target for cardiovascular disease management. Non-HDL cholesterol is a calculation of total cholesterol minus the cholesterol carried by HDL particles and comprises the cholesterol carried by all potentially atherogenic particles, including intermediate-density lipoproteins, very low-density lipoproteins, LDL cholesterol, chylomicrons, and remnant lipoproteins. Some meta-analyses showed that non-HDL cholesterol was more closely correlated with cardiovascular risk than LDL cholesterol, even at baseline and during therapy. So, since it reflects the full burden of the cholesterol transported in atherogenic lipoproteins, for being crucial in the prediction of cardiovascular disease risk and is closely associated with plaque progression, the purpose of using non-HDL cholesterol is to estimate the quantity of plasma-circulating atherogenic lipoproteins [43,44,45,46]. However, despite its importance in the diagnosis and treatment of dyslipidemia, non-HDL cholesterol is rarely reported in bariatric procedure clinical trials.
Apolipoprotein AI (apoAI) is the major component of antiatherogenic HDL cholesterol and apolipoprotein B100 (apoB100) is a major apolipoprotein found in all atherogenic lipoproteins. In numerous previous studies, high apoB100/apoAI ratios were identified as a risk factor for cardiovascular disease [47,48,49]. But, measuring apolipoprotein levels is very difficult and expensive. In clinical practice, the HDL cholesterol value reflects plasma apoAI levels and non-HDL cholesterol reflects plasma apoB100 levels. So, researchers have used new cardiovascular risk markers that have ratios with atherogenic components (which can reflect lipid profile, atherogenic balance, and lipoprotein metabolism) in the numerator and antiatherogenic components in the denominator. Thus, we decided to calculate the ratio between the measure of non-HDL cholesterol and HDL cholesterol, also called the “atherogenic coefficient”. This index was previously reported and, together with the other “lipoprotein ratios” or “atherogenic indices”, as they are often called, were superior to conventional lipid parameters as predictors of coronary artery disease [47]. Millán et al. described that the non-HDL cholesterol/HDL ratio is a linear combination of total/HDL cholesterol, and although few studies have evaluated this lipoprotein ratio for predicting cardiovascular disease, they can be assumed to be similar to those of the total/HDL cholesterol or LDL/HDL cholesterol ratios [13]. However, given the specificity of non-HDL cholesterol for atherogenic lipoproteins, we believe that this index is superior in the cardiovascular events risk analysis.
For the determination of HDL particle size, no statistically significant difference was observed between pre- and post-bariatric periods (p > 0.05). Although there is no consensus in the literature, studies suggest that bariatric surgery-induced alterations in the lipoprotein–lipid profile, associated with reduced cardiovascular risk, tend to increase the proportion of larger HDL subfractions (HDL2), which are more functional and possess atheroprotective properties compared to smaller ones. Additionally, a decrease in the smaller HDL subfractions (HDL3), which are considered less functional and more atherogenic, is often reported [50,51].
Despite slight variations in the reported values for HDL2 definition due to differences in separation methods, this subfraction is commonly characterized by a diameter between 8.8 and 13 nm. In the present study, preoperative particle diameters ranged from 10.34 to 14.85 nm, while postoperative values ranged from 9.946 to 14.34 nm, numerically consistent with the expected range for HDL2. Furthermore, individual analysis of particle sizes revealed a trend toward reduced HDL diameter in some patients (n = 8). This observation raises the hypothesis of a potential reduction in larger HDL subfractions (HDL2), which could potentially increase cardiovascular risk in these patients. However, it is crucial to note that this study did not employ separation methods to identify HDL subfractions, precluding the determination of the relative proportions of each. To test this hypothesis, the use of fractionation methods such as polyacrylamide gel electrophoresis or NMR spectroscopy is recommended.
In addition, the estimation of various atherogenic indices in patients undergoing bariatric surgery demonstrated a statistically significant decrease in the Castelli-I and -II indices and the Atherogenic Index of Plasma (AIP) following the procedure. Studies indicate that the Castelli-I and -II indices are important indicators of cardiovascular event risk, as they reflect the relationship between Apo-B-rich and Apo-A-rich lipoproteins [13,52]. The observed reduction in the Atherogenic Index of Plasma further supports an improved cardiovascular risk profile, as this index is associated with lower concentrations of pro-atherogenic lipoproteins and is considered a predictor of atherosclerosis risk [19]. The decrease in these indices post-surgery suggests a positive impact on cardiovascular health, potentially reducing the risk of atherosclerotic events in the postoperative period [53,54].
Continuing with the analysis of atherogenic indices, the size of LDL particles was estimated using the formula proposed by Maruyama, Imamura, and Teramoto [20], revealing a statistically significant increase after bariatric surgery. The median LDL particle size increased from 25.2 nm in the pre-bariatric period to 25.7 nm post-surgery.
Using NMR, LDL particles can be classified into four main subfractions based on their diameter: large LDL (26.0–28.5 nm), intermediate LDL (25.5–26.4 nm), small LDL (24.2–25.5 nm), and very small LDL (22.0–24.1 nm). From this perspective, considering a threshold of 25.5 nm to distinguish between atherogenic (small) and atheroprotective (large) particles, approximately 90% of patients (n = 24) had LDL particles classified as large LDL post-surgery. In contrast, only 30% of patients had LDL particle diameters exceeding 25.5 nm in the preoperative period. This increase in particle size may indicate a reduction in small and very small LDL particles, known for their high atherogenic potential, in favor of larger and less dense particles associated with lower cardiovascular risk [40,41,42].
In obese individuals, small LDL particles are commonly present due to the triglyceride exchange between VLDL and LDL particles, mediated by the cholesterol ester transfer protein, facilitating the formation of smaller, denser particles. These particles, when metabolized by hepatic lipase, are more susceptible to oxidative modification and endothelial penetration, triggering an inflammatory response and contributing to atherosclerosis development [38,42]. Thus, the observed modulation in LDL concentrations, coupled with an increase in LDL particle size after bariatric surgery, suggests an improvement in the lipid profile and atherogenic risk. This reduction in sdLDL particles, alongside an increase in larger, less dense particles, may reflect a decreased risk of atherosclerotic events. The reduction in vascular risk indices, in line with decreased LDL concentrations, further underscores the potential benefits of bariatric surgery in reducing cardiovascular risk in obese patients [55].
Although the present study estimated the mean LDL particle size, it is important to highlight that specific LDL subfractions were not identified. As with HDL, LDL subfraction separation could also be performed using techniques such as NMR or gel electrophoresis, allowing a more detailed evaluation of particles based on their density and size characteristics. This approach could provide a more precise understanding of changes in the lipid profile, particularly regarding LDL particles and their impact on atherogenic risk.
Moreover, the limitations of the methods used to calculate atherogenic indices should be acknowledged. While widely used due to their simplicity and low cost, these methods have limitations when applied individually to predict individual risk. Cardiovascular risk assessment based on atherogenic indices may overlook other important markers, such as systemic inflammation and insulin resistance, which also play a crucial role in cardiovascular pathophysiology [36].
In our study, when compared to the preoperative period, all calculated indices showed a significant decrease six months after the surgical procedure. For the Castelli index (the ratio of total/HDL cholesterol) and non-HDL/HDL cholesterol, we observed a significant increase one month after surgery. Although the non-HDL cholesterol absolute value did not present a significant difference during follow-up, the ratio using this value in the numerator showed a decrease in the first month, confirming the cardiovascular risk that patients undergoing bariatric surgery are exposed to at the beginning of the period postoperative. This risk is related to atherogenic particles, including intermediate-density lipoproteins, very low-density lipoproteins, LDL cholesterol, chylomicrons, and remnant lipoproteins. So, we conclude that substantial weight loss after bariatric surgery leads to improved lipid and glycemic profiles. However, it is very important to alert health professionals to monitor these individuals, especially during the first active weight loss phase, since cardiovascular risk increases in this phase.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/obesities5010005/s1, Table S1. General list of results obtained in samples from patients undergoing bariatric surgery in the pre- and postoperative period (1 year).

Author Contributions

Conceptualization, L.d.O.S.B. and F.B.F.-M.; methodology, L.d.O.S.B. and A.C.M.; software, B.F.N.; validation, L.d.O.S.B., A.C.M. and B.F.N.; formal analysis, B.F.N.; investigation, L.d.O.S.B. and A.C.M.; resources, F.B.F.-M.; data curation, B.F.N., A.C.R.d.M. and E.Q.d.A.M.; writing—original draft preparation, L.d.O.S.B.; writing—review and editing, A.C.R.d.M. and F.B.F.-M.; visualization, B.F.N.; supervision, F.B.F.-M. and E.Q.d.A.M.; project administration, F.B.F.-M.; funding acquisition, F.B.F.-M. All authors have read and agreed to the published version of the manuscript.

Funding

This study was provided by the Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC) (Grant 466/2016). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Institutional Review Board Statement

This study was conducted in accordance with the Declaration of Helsinki, and The Research by the Ethics Committee of the State University of Santa Catarina approved this study on human beings under the protocol 24279013.7.0000.0121.

Informed Consent Statement

Informed consent was obtained from all subjects involved in this study.

Data Availability Statement

The data underlying this article are available in the article and its online Supplementary Material. If further details are required, this information may be shared upon reasonable request to the corresponding author.

Acknowledgments

We would like to thank all the general practitioners, clinical pharmacists, pharmacy technicians from the Service of Clinical Analyses Laboratory from Hospital Universitário Polydoro Ernani de São Thiago—HU UFSC/EBSERH and all staff who helped in this study.

Conflicts of Interest

The authors declare no conflicts of interest.

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Figure 1. Fasting glucose (A), insulin (B), HDL cholesterol (C), non-HDL cholesterol, in subfigure C a red line was drawn to separate participants with HDL above and below 40 mg/dL (D), triglycerides (E), Castelli-I index (F), Castelli-II index (G), TG/HDL cholesterol (H) and non-HDL/HDL cholesterol (I) before, 1, 3, and 6 months after bariatric surgery. * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001.
Figure 1. Fasting glucose (A), insulin (B), HDL cholesterol (C), non-HDL cholesterol, in subfigure C a red line was drawn to separate participants with HDL above and below 40 mg/dL (D), triglycerides (E), Castelli-I index (F), Castelli-II index (G), TG/HDL cholesterol (H) and non-HDL/HDL cholesterol (I) before, 1, 3, and 6 months after bariatric surgery. * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001.
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Figure 2. HDL cholesterol levels are above and below the reference value percentage. RV: reference value. * p < 0.05; ** p < 0.01.
Figure 2. HDL cholesterol levels are above and below the reference value percentage. RV: reference value. * p < 0.05; ** p < 0.01.
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Figure 3. Results expressed in individual values and the median. (A) HDL particle size (nm); (B) individual analysis of HDL particle size; (C) PoI. Wilcoxon test was applied in (A,B), (p > 0.05). Source: Prepared by the author.
Figure 3. Results expressed in individual values and the median. (A) HDL particle size (nm); (B) individual analysis of HDL particle size; (C) PoI. Wilcoxon test was applied in (A,B), (p > 0.05). Source: Prepared by the author.
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Figure 4. Results expressed in individual values and the median. (A) LDL particle size (nm), (B) Atherogenicity Index of Plasma; (C) Castelli Index I; (D) Castelli Index II; Wilcoxon test. *** p < 0.05. Source: Prepared by the author.
Figure 4. Results expressed in individual values and the median. (A) LDL particle size (nm), (B) Atherogenicity Index of Plasma; (C) Castelli Index I; (D) Castelli Index II; Wilcoxon test. *** p < 0.05. Source: Prepared by the author.
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Table 1. Characteristics of patients.
Table 1. Characteristics of patients.
PreoperativePostoperative
(1 Month)
Preoperative
(3 Months)
Postoperative
(6 Months)
p-Value
Friedman Test
N82
Age (years)43 (21–62)
Female—No. (%)68 (83)
Male—No. (%)14 (17)
BMI (kg/m2)48 (34–71)42 (30–62)39 (29–56)34 (21–50)<0.0001 ****
Fasting glucose (mg/dL)104 (72–283)99 (78–219)92.5 (65–219)92 (66–184)<0.0001 ****
Insulin (µU/mL)23.8 (2–84)13.5 (4–42)11.7 (3–74)8.5 (3–35)0.0023 **
HDL-cholesterol (mg/dL)42 (20–58)34 (19–48)40 (23–60)43 (29–61)<0.0001 ****
Non-HDL-cholesterol (mg/dL)134.5 (75–238)111 (56–210)116 (50–190)114.5 (58–178)0.0753
TG (mg/dL)135 (54–423)135 (58–290)106 (52–190)90 (37–248)<0.0001 ****
AIP0.51 (−0.02–1.33)0.55 (0.08–0.98)0.42 (−0.05–0.77)0.31 (−0.12–0.80)<0.0001 ****
Castelli-I index4 (2–9)5 (3–11)4 (2–6)3 (2–5)0.0037 **
Castelli-II index3 (1–6)3 (1–9)3 (0.5–5)2 (1–4)0.0014 **
TG/HDL-cholesterol3 (1–21)4 (1–10)3 (1–6)2 (1–6)<0.0001 ****
n-HDL/HDL-cholesterol3 (1–8)4 (2–10)3 (1–5)2 (1–4)<0.0037 **
LDL size (nm)25 (19–26)25 (23–26)25 (24–26)26 (24–26)<0.0001 ****
Results are presented as median values (minimum–maximum range). BMI: body mass index; HDL: high-density lipoprotein; TG: triglycerides; AIP: Atherogenic Index of Plasma; LDL: low-density lipoprotein. ** p < 0.01, **** p < 0.0001.
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Bratti, L.d.O.S.; Martins, A.C.; Nunes, B.F.; Moura, E.Q.d.A.; Moraes, A.C.R.d.; Filippin-Monteiro, F.B. Cardiovascular Risk Assessment in the Immediate Postoperative Period of Bariatric Surgery. Obesities 2025, 5, 5. https://doi.org/10.3390/obesities5010005

AMA Style

Bratti LdOS, Martins AC, Nunes BF, Moura EQdA, Moraes ACRd, Filippin-Monteiro FB. Cardiovascular Risk Assessment in the Immediate Postoperative Period of Bariatric Surgery. Obesities. 2025; 5(1):5. https://doi.org/10.3390/obesities5010005

Chicago/Turabian Style

Bratti, Letícia de Oliveira Souza, Ana Carolina Martins, Bruno Fonseca Nunes, Emerita Quintina de Andrade Moura, Ana Carolina Rabello de Moraes, and Fabíola Branco Filippin-Monteiro. 2025. "Cardiovascular Risk Assessment in the Immediate Postoperative Period of Bariatric Surgery" Obesities 5, no. 1: 5. https://doi.org/10.3390/obesities5010005

APA Style

Bratti, L. d. O. S., Martins, A. C., Nunes, B. F., Moura, E. Q. d. A., Moraes, A. C. R. d., & Filippin-Monteiro, F. B. (2025). Cardiovascular Risk Assessment in the Immediate Postoperative Period of Bariatric Surgery. Obesities, 5(1), 5. https://doi.org/10.3390/obesities5010005

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