Characterization of patients with acute idiopathic pancreatitis using an administrative claims database in Japan

Abstract

Background: Hypertriglyceridemia is one of the causes of idiopathic acute pancreatitis and atherosclerotic cardiovascular diseases. Most guidelines define fasting triglyceride levels greater than 150 mg/dL as hypertriglyceridemia; however the triglyceride level of patients with acute pancreatitis is not clear, nor is it known how much triglyceride level reduction can reduce cardiovascular events. This study aimed to characterize patients with acute idiopathic pancreatitis and especially focused on triglyceride levels, patient characteristics, pharmaceutical treatment, and prognosis.

Methods: In this retrospective analysis of an administrative claims database, patients hospitalized due to acute pancreatitis were selected, and idiopathic pancreatitis was identified using specific pre-determined ICD-10 codes. A Wilcoxon rank sum test was performed for the comparison of the means of the two cohorts, and Fisher's exact test was used to compare proportions between the cohorts. The comparison between idiopathic and non-idiopathic pancreatitis was performed using a log-rank test.

Results: Between April 1, 2008, and July 31, 2021, 44,005 patients were hospitalized for the treatment of pancreatitis; among them, 30,814 cases (70.0%) were categorized as idiopathic. The mean age of patients with idiopathic pancreatitis was 62.7±18.8 years, 68.8% of the patients were male, and the mean triglyceride levels within 3 days after hospitalization were 293.1±816.6 mg/dL. Rehospitalization due to recurrent pancreatitis and the incidence rates of cardiovascular events were 39.5% and 3.3%, respectively.

Conclusions: Patients with idiopathic pancreatitis had elevated triglyceride levels at admission. Even if triglyceride levels are not extremely high, hypertriglyceridemia might cause idiopathic pancreatitis. Therefore, there is a need for intervention in terms of triglyceride levels in patients with hypertriglyceridemia, not only to prevent cardiovascular disease, but also to prevent the onset and recurrence of acute pancreatitis.

Trial registration: Not applicable

Background

Hypertriglyceridemia (HTG) is one of the major causes of cardiovascular (CV) events and acute pancreatitis [1-5]. It is the third most common cause of acute pancreatitis, following alcoholic pancreatitis and gallstone pancreatitis, accounting for 12–22% of all cases; however, the incidence rate and rank order of each type of pancreatitis varies depending on the country [6-10]. HTG includes secondary HTG, which is caused by overeating, transient heavy alcohol consumption, diabetes mellitus, or obesity, resulting in increased lipid synthesis in the liver [11,12] Primary HTG is caused by a deficiency or dysfunction of intrinsic factors, such as lipoprotein lipase, ApoC II, and angiopoietin-like protein-3 [13,14]. In some cases, such as hereditary familial hyperchylomicronemia, the serum triglyceride (TG) level may exceed 1000 mg/dL [15]. According to cholesterol management guidelines for preventing atherosclerotic CV diseases [16-18], HTG is defined as a fasting serum TG level of 150 mg/dL or higher. A fasting serum TG level of 500 mg/dL or higher is considered a severe case requiring specialist referral [16]. Dietary therapy, aimed at caloric and fat intake restriction, and pharmacological therapy are used to prevent the onset of acute pancreatitis [19-21], especially in severe HTG. However, the threshold of TG levels that increase the risk of developing acute pancreatitis, TG levels requiring aggressive therapeutic intervention, and target therapeutic levels remain unclear. In addition, chronic HTG is a risk factor for CV events [2,3]. 

In this study, we aimed to clarify (1) patient background including TG levels at the time of admission for acute pancreatitis, and the rate of recurrent acute pancreatitis; and (2) the rate of coronary artery disease (CAD) events, stroke events, and death in patients hospitalized for idiopathic pancreatitis using administrative claims data.

Methods

Study design

This was a retrospective database study that utilized administrative claims data obtained from Medical Data Vision Co. Ltd. (MDV; Tokyo). The database provides claims data from 399 hospitals (approximately 30 million patients, as of February 2020) using the Diagnosis Procedure Combination (DPC) system (29.6% of general hospitals and 54.1% of general beds in Japan that employ the DPC system, as of March 2019) and available medical information of inpatients and outpatients in these hospitals. This study was conducted in fully compliant with the Declaration of Helsinki and the Ethical Guidelines for Medical and Health Research Involving Human Subjects, a local guidelines issued by Ministry of Health, Labor and Welfare (“The Ethical Guidelines”). The requirement for informed consent and ethics approval were not required for this study as unlinkable anonymized data were used, in accordance with the “Ethical Guidelines”.

Study population

Of the registered patients in the MDV database, those who received a confirmed diagnosis of acute pancreatitis between April 1, 2008, and July 31, 2021, and were hospitalized for the treatment of pancreatitis (for hospitalized patients, “pancreatitis” was a trigger in the DPC coding data) were identified as having acute pancreatitis. The following patients were excluded from the study: 1) those with insufficient demographic and clinical information in an up to 180-day baseline period before the onset of pancreatitis, 2) those who were hospitalized with pancreatitis, but were not confirmed to have pancreatitis during their hospitalization and were presumed to have been hospitalized due to other diseases, 3) those whose confirmed diagnosis of pancreatitis was made on or after the third day of hospitalization (because the possibility of developing acute pancreatitis after hospitalization cannot be excluded), and 4) those with pancreatic cancer or a history of pancreatic cancer.

Definitions of pancreatitis

Pancreatitis was defined using the International Statistical Classification of Diseases and Related Health Problems, 10th version (ICD-10) codes, and classified into two categories: 1) idiopathic pancreatitis, which includes pancreatitis with an unidentified etiology and alcoholic pancreatitis (K852 and K860), and 2) non-idiopathic pancreatitis, which includes viral pancreatitis, gallstone pancreatitis, drug-induced pancreatitis, post-endoscopic retrograde cholangiopancreatography/postoperative pancreatitis, and autoimmune pancreatitis (Table 1). Alcoholic pancreatitis was included under idiopathic pancreatitis because excessive alcohol intake may directly affect the pancreas in some patients or result in excess caloric intake or hepatic injury leading to metabolic abnormalities in other patients. Gallstone pancreatitis was identified from the patient code K851, or when a patient hospitalized due to pancreatitis underwent any of the treatment procedures for cholelithiasis (K682-3, K6851, K6852, K686, K6861, K6871, K6872, K6874, K688, and K699-21) during hospitalization. 

<Insert Table 1 here>

Data acquisition

The index date was defined as the date that pancreatitis was diagnosed or after the date of admission. Up to 180 days prior to the index date was the baseline period for obtaining patient background information. In some cases, such as emergency admission, the 180-day baseline period may have been unavailable. However, a patient was included in the study if sufficient patient background information was available from the admission record. Admission laboratory values were used if available. If data from the day of admission were unavailable, the maximum values, within 3 days after the day of admission, were used. TG values at or within 3 days after discharge were used to determine the status of each patient at the time of discharge. If there were multiple laboratory values at admission or discharge, the highest value was used. Few patients had laboratory values, accounting for less than 10% of eligible patients. All drugs used for the treatment of pancreatitis and HTG/dyslipidemia during hospitalization were identified using specific drug codes. 

Outcomes

Patient outcomes investigated in this study were recurrent pancreatitis, CV events, and total mortality. The recurrence of pancreatitis was defined as rehospitalization for pancreatitis after discharge from the index hospitalization, and the time to the date of rehospitalization was evaluated. Hospitalization due to CAD (I20, I21, and I22) and stroke (I60, I61, I62, and I639) after discharge from the index hospitalization was defined as the incidence of CV events, and the time to CV event–related hospitalization from the index hospitalization to the day of discharge was investigated. Death was defined as any cause of death after discharge from the index hospitalization. Time to death was additionally investigated.

Statistics

Patient background and laboratory data are expressed as mean ± standard deviation or patient proportion (%). A Wilcoxon rank sum test was performed for the comparison of the means of the two cohorts, and Fisher's exact test was used to compare proportions between the cohorts.

Patient outcomes (recurrent acute pancreatitis; CV events, including CAD and stroke; and death) were evaluated as incidence rates in 1000 person-years. The time-to-event from the index date was shown using Kaplan–Meier (KM) curves, and incidence rates and their 95% confidence intervals were estimated at days 30, 60, 90,180, 360, 720, 1080, 1440, and 1800. The follow-up period was ended at day 3600 from the index date. The comparison between idiopathic and non-idiopathic pancreatitis was performed using a log-rank test, and P<0.05 was considered statistically significant.

Data collection, quality control, and statistical analysis were performed by Medical Data Vision, Co. Ltd. and MediStatLab, Co. Ltd. (Tokyo Japan). All tabulations and analyses were performed using R 3.5.3 (R Foundation for Statistical Computing, Vienna, Austria).

Results

Baseline clinical and demographic characteristics of patients with acute pancreatitis

In total, 52,525 patients who hospitalized due to treatment of pancreatitis were identified. After excluding 8,520 patients who did not meet the study criteria, totaling 44,005, were included in the analysis. 2,062 patients with laboratory test values were also analyzed for admission laboratory values (Fig. 1). 

<Insert Figure1 here>

The characteristics of patients with idiopathic and non-idiopathic pancreatitis are presented in Table 2. The proportion of men was 68.0% in idiopathic patients and 56.5% in non-idiopathic patients (P<0.001). The mean age in the idiopathic and non-idiopathic cohorts was 59.6±19.2 and 69.9±15.6 years, respectively (P<0.001 vs. idiopathic cohort). The number of patients with idiopathic pancreatitis gradually increased from the late teenage years and remained constant from ages 40 to 80 years, whereas the number of patients with non-idiopathic pancreatitis gradually increased from the late 20s and peaked at 70 years (Figure 2). Of the patients with idiopathic pancreatitis, 23.0% had alcoholic pancreatitis. Gallstone pancreatitis accounted for 88.8% of non-idiopathic pancreatitis, followed by autoimmune pancreatitis (10.9%). A history of stroke or CAD, and metabolic diseases—such as dyslipidemia, diabetes mellitus, and hypertension—were more common in patients with non-idiopathic pancreatitis. Concomitant medications at the time of admission (i.e., medicines prescribed before the onset of acute pancreatitis) were more common in patients with non-idiopathic pancreatitis. Medicines for dyslipidemia were not commonly prescribed during the baseline period (i.e., before the index date) in either cohort. Statins were administered in 5.2% and 7.6% of patients with idiopathic and non-idiopathic pancreatitis, respectively. The prescription of other anti-dyslipidemia medicines, such as pemafibrate, proprotein convertase subtilisin kexin 9 inhibitors, and eicosapentaenoic acid (EPA), was limited in both patient cohorts. 

<Insert Table 2 here>

Laboratory values at the onset of acute pancreatitis

Laboratory values, which were available for 2,062 patients during the index hospitalization, are shown in Table 3. The mean TG values within 3 days after admission (days 0–2) were 293.1±816.6 and 102.7±174.5 mg/dL in patients with idiopathic and non-idiopathic pancreatitis, respectively; the values were significantly higher in patients with idiopathic pancreatitis (P<0.001). Given the large standard deviation values, it was expected that some patients would have very elevated TG values. Therefore, we studied the distribution of TG levels; the results are presented in Figure 3. In patients with idiopathic pancreatitis, 5% had a TG level of 1000 mg/dL or higher, with a maximum value of 3,426 mg/dL in patients with non-idiopathic pancreatitis and 11,060 mg/dL in patients with idiopathic pancreatitis. TG levels below 150 mg/dL (P<0.001) were observed in 89.3% and 70.4% of patients with idiopathic and non-idiopathic pancreatitis, respectively.

<Insert Table 3 here>

The mean values of low-density lipoprotein cholesterol (LDL-C) and hemoglobin A1c were in the normal range in both cohorts; however, the mean values of blood amylase, C-reactive protein (CRP), and white blood cell (WBC) count were significantly higher than the upper limit of the normal range (normal ranges for amylase, CRP, and WBC are 44–132 U/L, < 0.14 mg/dL, and 3.3–8.6 × 10⁹/L, respectively.)

Pharmacological treatment during hospitalization

Drug therapy for pancreatitis during hospitalization was investigated. Protease inhibitors were prescribed to more than 80% of patients with idiopathic and non-idiopathic pancreatitis. The number of patients who were newly prescribed anti-dyslipidemia medicine after the onset of pancreatitis was small: in patients with idiopathic and non-idiopathic pancreatitis, statins were prescribed to 8.0% and 13.0% (P<0.001), ezetimibe to 1.0% and 1.2% (P=0.228), fibrates to 1.9% and 1.5% (P=0.003), pemafibrate to 0.5% and 0.2% (P<0.001), nicotinic acid to 0.4% and 0.6% (P=0.015), and EPA to 1.5% and 1.3% (P=0.128), respectively(Table 4).

<Insert Table 4 here>

Recurrence of pancreatitis

Rehospitalization for recurrent pancreatitis occurred in 6,055 patients with idiopathic pancreatitis and in 1,822 patients with non-idiopathic pancreatitis, and no differences in rehospitalization rate due to recurrent pancreatitis were observed between the two patient cohorts up to 180 days after the date of discharge from the index hospitalization. The recurrence rate was 13.0% in patients with idiopathic pancreatitis and 12.6% in patients with non-idiopathic pancreatitis, which was similar. After 180 days, the difference in rehospitalization rates due to recurrent pancreatitis between the idiopathic and non-idiopathic cohorts increased to 19.9% and 16.0% at 360 days and 39.5% and 22.8% at 1,800 days, respectively (P<0.001) (Figure 4a).

CAD, stroke, and all-cause mortality events

Hospitalizations due to the incidence of CAD events occurred in 385 patients with idiopathic pancreatitis and 167 patients with non-idiopathic pancreatitis. The incidence rates were similar at day 1800, at 3.3% in idiopathic and 3.5% in non-idiopathic pancreatitis cases. There were no significant differences in the recurrence rate between the cohorts by day 3600 (P=0.825) (Figure 4b). The incidence of CAD events was significantly lower than that of rehospitalization for recurrent pancreatitis.

Hospitalization due to stroke occurred in 302 and 151 patients with idiopathic and non-idiopathic pancreatitis, respectively. The incidence rates were 2.8% and 3.0% for patients with idiopathic and non-idiopathic pancreatitis, respectively, at 1800 days, and were lower than those for rehospitalization due to recurrent pancreatitis and similar to those for hospitalization due to CAD events. The rates derived from the KM curves were almost identical up to 360 days, whereafter they were higher in the non-idiopathic cohort; however, they were similar at 1800 days, and marginally higher thereafter (P=0.089) (Figure4c).

All-cause mortality occurred in 1,265 patients with idiopathic pancreatitis and 566 patients with non-idiopathic pancreatitis. The mortality rates were similar at 1800 days—10.4% in the idiopathic cohort and 11.3% in the non-idiopathic cohort—and were lower than those for rehospitalization for pancreatitis, and higher than those for CV and cerebrovascular disease. The KM curves were almost identical up to 720 days; thereafter, the rates derived for the non-idiopathic cohort tended to be marginally higher (P=0.258) (Figures 4d).

Discussion

In this study, patients with idiopathic pancreatitis had elevated TG levels at admission. Furthermore, patients with idiopathic pancreatitis had a higher rate of recurrent acute pancreatitis. To our knowledge, this is the first study to clarify TG levels in the acute phase of non-idiopathic pancreatitis, suggesting the need for early therapeutic intervention in patients with high TG levels.

In Japan, a survey conducted by the Research and Study Group of the Ministry of Health, Labour and Welfare (MHLW) in 2011 reported that the incidence rate among 63,080 patients who received treatment for acute pancreatitis in one year was 49/100,000 persons/year, with a male-to-female ratio of 1.9:1 and a mean age of 65.3±19.6 years [22]. Similarly, other epidemiological studies have shown that the incidence was higher in men and that the number of patients was higher in the 60–70-year age group [23]. Although some types of pancreatitis can be treated on an outpatient basis depending on severity, this is a disease that requires inpatient care, as per the treatment guidelines of Japan [17] and the USA [24]. In this study, only patients with pancreatitis that required inpatient care were eligible. Compared to the MHLW survey, this study may have included patients with more severe pancreatitis; however, no significant differences in the age of onset or sex were observed.

In this study, gallstone pancreatitis accounted for 26.6% of all cohorts and 88.8% of the non-idiopathic pancreatitis cohort. This may have resulted from a lower incidence rate of cholelithiasis in Japanese patients [25] compared with that in Caucasian patients [26]. Alcoholic pancreatitis accounted for 16.1% of all cohorts and 23.0% of the idiopathic cohort, which is similar to the findings of UK studies [1]. More than 50% of all patients with pancreatitis had an unknown etiology in this study. The reason for this was unclear. The idiopathic-to-non-idiopathic pancreatitis ratio was 3:7 in this study, which is similar to that found in UK studies (20–34%) [6].

There was a difference in age distribution between patients with idiopathic and those with non-idiopathic pancreatitis, which  was thought to be influenced by the underlying disease. Idiopathic pancreatitis, as represented by alcoholic pancreatitis, was thought to be caused by metabolic abnormalities resulting from alcohol consumption, dietary habits, and accumulated damage to the liver and pancreas. Therefore, it is likely that pancreatitis develops at a relatively young age due to binge drinking and overeating in the late teenage years or later. In contrast, gallstone pancreatitis accounts for approximately 90% of non-idiopathic pancreatitis. As the age of onset of cholelithiasis is 60–70 years [27], the distribution may be due to the occurrence of this disease.

The average TG value within 3 days (days 0–2) after admission due to acute pancreatitis was 293.1±816.6 mg/dL for idiopathic pancreatitis. The incidence of severe HTG exceeding 500 mg/dL was less than 10%; however, approximately 30% of patients had a value that fit the definition of HTG of more than 150 mg/dL. The prevalence of dyslipidemia, which included patients with familial hyperlipidemia, was 21.6% at baseline. This value is similar to that reported previously (15–20% of all subjects referred to Lipid Clinics) [9]. Whether HTG directly triggers acute pancreatitis is unknown due to the inability to confirm a causal relationship in the DPC system and claims data and the absence of an equivalent injury or disease code for “HTG-induced acute pancreatitis.” In addition, as excessive alcohol consumption can cause HTG and affect the liver and pancreas, some patients who have been classified as having alcoholic pancreatitis may have had HTG as well. Nevertheless, the present results show that TG levels were higher in patients with idiopathic pancreatitis than in those with non-idiopathic pancreatitis, suggesting that HTG may play some role in the development of idiopathic pancreatitis.

In terms of drug therapy for pancreatitis during hospitalization, statins were used in 8.0% and 13.0% of patients with idiopathic and non-idiopathic pancreatitis, respectively. Moreover, fibrates, pemafibrate (known as a selective peroxisome proliferator-activated receptor α modulator), and EPA were infrequently used in patients with idiopathic pancreatitis. Since TG levels can be reduced rather effectively by fasting, it is possible that aggressive pharmacotherapy against HTG is not conducted during hospitalization. This may be influenced by the fact that the acute phase of pancreatitis, just after the onset, is devoted to acute treatment, and that treatment strategies for lowering TG levels, other than fasting, are not always available. A more detailed study of the risk of developing acute pancreatitis due to dyslipidemia, especially HTG, is warranted.

The recurrence rate of acute pancreatitis is known to vary depending on factors such as the cause and treatment [28]. In this study, there were no differences in the recurrence rates between the idiopathic and non-idiopathic pancreatitis cohorts up to 180 days; however, the differences between the two cohorts increased thereafter, showing significantly different prognoses. This is because the cause of non-idiopathic pancreatitis, such as gallstones, is often clearly known; the cause can be treated; or the disease can be managed continuously, such hereditary pancreatitis. In contrast, idiopathic pancreatitis is difficult to chronically manage to prevent recurrence because the cause of the disease is unclear and the patients’ lifestyle habits, such as excessive alcohol and fat intake, are involved. Although lifestyle intervention leads to a temporary improvement in diet, patients' lifestyles may revert over time. In addition, while statins are very effective in lowering LDL-C levels, they may not always effectively lower TG levels.

The incidences of CAD and stroke did not differ between non-idiopathic and idiopathic pancreatitis. As HTG is a risk factor for acute pancreatitis and atherosclerosis [2,3,29], treatment for patients with HTG should focus on preventing acute pancreatitis and CV events. Particularly, for patients with severe HTG, even if acute pancreatitis can be prevented using dietary restriction and drug therapy, the risk of atherosclerosis may not be adequately controlled because the threshold for CV events and acute pancreatitis may differ from mild-to-moderate HTG. If chronic, atherosclerosis and atherosclerotic CV events may be induced [30,31]. Although using statins to lower LDL-C levels is a standard therapy for preventing CV events in current clinical practice, there is a residual risk for atherosclerotic CV events that remains even when LDL-C levels are sufficiently lowered, and one of the causes underlying the risk is HTG [32,33]. TG-rich lipoproteins, such as intermediate density lipoproteins, very low-density lipoproteins, and remnants may promote atherosclerosis development by a different mechanism from that of LDL-C [34,35]. It has been suggested that lowering atherogenic TG-rich particles other than LDL-C may be important for preventing CV events in patients with HTG.

In this study, approximately 30% of patients with idiopathic pancreatitis had TG levels of 150 mg/dL or higher and the incidence rate of CAD or stroke was approximately 3%, which was significantly lower than that of recurrent pancreatitis. Further investigation on the incidence of CV events in patients with higher serum TG values among those with idiopathic pancreatitis is required in the future.

Limitations

First, few patients registered in the MDV database have available laboratory values, such as TG, and in the patients with available TG values, it is unknown whether the TG levels are measured immediately after the onset of acute pancreatitis. Because TG levels can easily fluctuate under the influence of diet and other factors and can decrease significantly after several hours of fasting, it was not possible to accurately determine TG levels at the onset of acute pancreatitis in this study. TG levels have been shown to be high in patients with idiopathic pancreatitis; however, we could not analyze the threshold level at which the risk of developing acute pancreatitis increased.

Second, urgent cases brought to the emergency department may have been excluded from the analysis because of insufficient available patient background information, and severe cases may also have been excluded.

Third, in this study, idiopathic pancreatitis included patients whose data included alcoholic pancreatitis as a disease name. Alcoholic pancreatitis should be excluded from idiopathic pancreatitis if alcohol is a clear cause; however, it is difficult to determine whether alcohol is the direct cause in many cases. Therefore, alcoholic pancreatitis was included in the idiopathic pancreatitis category in this study to account for this; however, it is unclear how this may have affected the results.

Last, the time from the onset of acute pancreatitis to hospitalization may vary among patients, and the exact time could not be obtained. This may have affected the study results, particularly the laboratory test values.

Conclusions

Hypertriglyceridemia is one of the causes of idiopathic acute pancreatitis and atherosclerotic CV diseases. However the TG level of patients with acute pancreatitis is not clear, nor is it known how much TG level reduction can reduce CV events. In this study, the characteristics of patients with acute pancreatitis and the incidence of events after discharge were studied. Patients with idiopathic pancreatitis had high TG levels at admission and LDL-C levels within the normal range, and few patients were treated with lipid therapy during hospitalization. The rate of acute pancreatitis recurrence after discharge was high. More detailed studies and treatment strategies for idiopathic pancreatitis are warranted for each cause of the disease.

Abbreviations

CV, cardiovascular; TG, triglycerides; HTG, hypertriglyceridemia; CAD, coronary artery disease; MDV, Medical Data Vision Co. Ltd.; DPC, Diagnosis Procedure Combination; EPA, eicosapentaenoic acid; LDL-C, low-density lipoprotein cholesterol; CRP, C-reactive protein; WBC, white blood cell; KM, Kaplan–Meier; MHLW, Ministry of Health, Labour and Welfare

Declarations

Ethics approval and consent to participate: 

This study was conducted in fully compliant with the Declaration of Helsinki and the Ethical Guidelines for Medical and Health Research Involving Human Subjects, a local guidelines issued by Ministry of Health, Labor and Welfare (“The Ethical Guidelines”). According to the Ethical Guidelines, the studies the approvals by the independent According to the Ethical Guidelines, retrospective studies using anonymized, structured data, 1) do not require the approvals from institutional review boards (IRB) or independent ethical committees (IEC) and 2) do not necessarily require informed consent from individual patients. Therefore, in accordance with the Ethical guidelines, IRB or IEC approval and patient consent regarding data usage were not obtained in this study.

Consent for publication: 

Not applicable.

Availability of data and materials:

The datasets generated and/or analyzed during the current study are not publicly available due to licensing agreements with Medical Data Vision Co., Ltd. Please contact Miki Imura, the corresponding author of this paper, for data availability.

Competing interests: 

The authors declare that they have no competing interests.

Funding: 

The design of the study, data analysis, interpretation of the data and the writing of the manuscript were conducted by Pfizer Japan Inc. The data acquisition, data analysis, English editing of the manuscript and publication were solely funded by Pfizer Japan Inc. No external grants were used.

Authors’ contributions: 

MI and JK contributed to the development of the study concept, the study design, the interpretation of the study results, and the writing of the manuscript. All authors read and approved the final manuscript.

Acknowledgements:

The authors would like to thank the participants of the study. The authors are grateful to Medical Data Vision Co. Ltd. for advice on dataset preparation, Dr. Shimamoto from MediStatLab Co., Ltd. for assistance with statistical analysis, and Editage (www.editage.com) for English language editing.

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Tables

Table 1 Category of pancreatitis

Table 2 Patient characteristics

*P values of comparison between the idiopathic and non-idiopathic cohorts

Abbreviations: SD, standard deviation; ACEi, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; NSAIDs, non-steroidal anti-inflammatory drugs; PCSK9, proprotein convertase subtilisin kexin 9; EPA, eicosapentaenoic acid.

Table 3 Laboratory values at baseline, admission, and discharge

*P values of comparison between the idiopathic and non-idiopathic cohorts

Abbreviations: TG, triglyceride; SD, standard deviation; HbA1c, Hemoglobin A1c; CRP, C-reactive protein; WBC, white blood cell.

Table 4 Pancreatitis-related drugs prescribed during hospitalization

Drugs prescribed for treatment of pancreatitis and dyslipidemia during admission are studied.

*P values of comparison between the idiopathic and non-idiopathic cohorts

Abbreviations. PCSK9, proprotein convertase subtilisin kexin 9; EPA, eicosapentaenoic acid.