In this study, we evaluated the relationship between lipid levels at the time of admission and hospital mortality in patients with AP. We found that higher H/L ratio levels were positively correlated with increased mortality in patients with AP, and determined the optimal cutoff for using the H/L ratio to assess AP-related mortality. The main results from this study indicate that the H/L ratio can be used to predict outcomes in patients with AP. To the best of our knowledge, this is the first study to confirm the predictive value of the H/L ratio and analyze the accuracy of this indicator in patients with AP.
Cholesterol is a structural component of cell membranes and is localized in membrane micro-domains that assemble signal transduction machinery. It is associated with proteins involved in key cell signaling pathways that are closely related to inflammation [8, 12]. There are five major lipoproteins: chylomicrons and very low-density lipoprotein, medium-density lipoprotein, low-density lipoprotein and high-density lipoprotein, which are classified compared with the density of the surrounding water [13, 14]. To facilitate cell absorption and utilization of fat through receptor-mediated endocytosis, LDL carries all of the fatty molecules, cholesterol, phospholipids and triglycerides, while HDL transports cholesterol from the cells and tissues back to the liver [15]. Rather than measuring actual HDL and LDL particles, assessing HDL-C and LDL-C levels provides information about how much cholesterol is delivered by all HDL and LDL particles. HDL and LDL oxidation is associated with an increased risk of developing cardiovascular disease because the oxidized forms are more susceptible to proteoglycan [16].
The relationship between HDL-C, LDL-C and cardiovascular disease has been well established over the years. Many guidelines recommend lowering LDL-C to reduce the risk of coronary heart disease, and highlight the protective role of HDL-C [17]. Given the essential function of blood lipids, LDL-C and HDL-C levels can be used to predict mortality not only in patients with cardiovascular disease but also in patients with colorectal cancer [18]. Although pancreatic exocrine function is directly linked to lipid metabolism, little is known about the predictive value of HDL-C and LDL-C in patients with AP.
In this retrospective study, we analyzed medical records from 166 patients with AP, who were admitted to the ICU for organ support, and evaluated the role of LDL-C and HDL-C levels and H/L ratios in predicting mortality in these patients. Interestingly, we found that the HDL-C/LDL-C ratio is a potential biomarker, and is more sensitive and specific than lactate, a biomarker that is widely recognized as a marker of mortality in critically ill patients [9].
The mechanism of the relationship between H/L ratios and AP prognosis is not clear, but there are several plausible explanations. Some studies have shown that there is some correlation between serum lipid levels and nutritional status, and the predictive value of H/L ratios could therefore be attributable to the nutritional status of patients with AP [9, 19]. However, there was no difference in serum albumin levels between survivors and non-survivors in our study. Therefore, it is unlikely that the different H/L ratios observed in these patients were related to nutritional status. Besides, we observe a inconsistent trend of cholesterol levels and triglyceride level in our cohort. Since cholesterol has an impact on maintaining vascular integrity and LDL-C levels can alter platelet acceptability through their effects on platelet activating factor, we hypothesize that the H/L ratio has a more complex role in AP progression, and believe that further research regarding this role is urgently needed.
AP may be caused by several factors. Gallstones and alcohol abuse are long-term risk factors, although hypertriglyceridemia is more common in China than alcohol abuse [20]. The method most commonly used to measure LDL-C is the Friedewald equation. Various confounding laboratory abnormalities can be present in patients with AP, especially in those with hypertriglyceridemia pancreatitis, and LDL-C levels are still the main target for treatment in patients with hyperlipidemia and the primary factor on which most of our clinical decisions are based [13]. In addition, in patients with simple gallstone AP, H/L ratios were still significantly different between survivors and non-survivors, suggesting that our conclusion is not related to AP etiology.
We compared the predicted values of common predictive indicators and the H/L ratio. In our study, H/L ratio had a higher predictive value than PCT, CRP or IL-6. Recently, several studies with small sample sizes reported that low levels of HDL-C are associated with high risk of persistent organ failure in AP [21]. Our study confirmed that HDL-C levels could be a predictor for patients with AP, and we found that the H/L ratio had a better predictive value than HDL-C levels. However, we found lower HDL-C is beneficial for patients, which is consistent with other studies [22, 23]. One explanation is that due to the retrospective study design, the lipid status parameters in our study are influenced by some patients leading to the distribution of our data is unlikely with others. In the future we still need more well-designed research to clarify relationships between HDL-C and AP mortality.
Our study had several limitations. First, because of the small sample size and the retrospective evaluation of cases, selection bias may have affected the generalizability of our results. Second, since this was an observational single-center study, the causal role of LDL-C in AP requires further investigation in prospective multicenter validation studies. In addition, we only examined one-time measurements. Therefore, this study did not address the issue of HDL-C and HDL-C variation in individuals. We use morality as our primary outcome instead of organ failure assessment which is not available for all patients because of the study design though it is not an indicator early enough for AP patients’ stratification in the ICU. There is an urgent need to obtain additional prospective data in consecutive patients to confirm our findings.