Sepsis is a clinical syndrome with high mortality, involves biochemical and physiological abnormalities caused by a dysregulated inflammatory response to infection [1]. The mortality rate of patients diagnosed with sepsis is between 20% to 50% and one of the leading causes of death among patients in Intensive Care Units (ICUs) [2]. Sepsis is associated with many serious metabolic changes. Based on these changes, many prognostic factors have been tried to be determined for sepsis patients including inflammatory cytokines (e.g., tumor necrosis factor, interleukins, C-reactive protein), procalcitonin, bilirubin, plasma lipids and lipoproteins. Also, scoring systems are used to predict disease severity and mortality in intensive care patients with sepsis. The Acute Physiology and Chronic Health Evaluation 2 (APACHE-2) scoring system is the most used scoring system in the World for ICU patients. Also, the Sequential Organ Failure Assessment (SOFA) scoring system is used to diagnose sepsis patients in the ICU and determine their prognosis [3,4].

Atherosclerotic Cardiovascular Diseases (ASCVD) are the main cause of premature death in developed and developing countries. Among the many preventable risk factors that increase the risk of ASCVD, the most important is dyslipidemia. Because dyslipidemia is the main factor in the pathogenesis of atherosclerosis, it is very common and has an asymptomatic course [5,6]. When compared in all age groups, Triglycerides (TG) increase with age and reach their maximum values between 50-59 years of age in men and 60-69 years of age in women. The increase in Low-Density Lipoprotein Cholesterol (LDL) levels is associated with age. No changes were observed in High-Density Lipoprotein Cholesterol (HDL) levels with aging [7].

As a result, the mortality rate increases in both old age and sepsis. We planned to do this study in the group of geriatric septic patients with high mortality rates. We also investigated the relationship between lipid profiles and mortality among this group of patients. The scoring systems used worldwide for prognostic evaluation of patients with sepsis were also evaluated in our study.     

This retrospective study was conducted of patients in the medical Intensive Care Unit (ICU) of Adana City Training and Research Hospital. Sepsis was identified in accordance with the guidelines of the Third International Consensus Definitions for Sepsis and Septic Shock [8]. All patients aged >64 years who met the criteria were included in the study. The data were obtained from the hospital system. Patients with cancer, patients with covid-19 and patients who could not obtain the necessary data for the study were excluded from the study. As a result, 88 patients were included in the study. The results of the biochemical and hematological analyses and the clinical results of the patients were obtained from the patient files in the hospital database.

Statistical Analysis

Statistical analyses were made using R version 3.4.2 (R Foundation for Statistical Computing, Vienna, Austria) software. Continued variables were tested for normal distribution. Normally distributed variables are expressed as average Standard Deviation (SD), while normally undistributed variables are reported as median and Interquartile Ranges (IQR). Categoric variables such as Number (n) and percentage (%). Continuous inter-group variable comparisons were performed using the student t-test or Mann Whitney U-test. Groups were compared based on categorical variables using the chi-square test or the Fisher Exact test. A univariate logistic regression analysis was conducted to evaluate the relationship between variables and mortality. All variables that were statistically significant for mortality were included in the univariate analysis and all variables with a P value <0.2 in the univariate analysis were included in the multivariate analysis with the backward stepwise method for the prediction of mortality.

The study was performed 88 patients, including 47 (53.4%) males with an average age of 75.2 8.2 years and 41 (46.6%) females with an average age of 75.4 7.8 years. The survivors group included 58 patients and non-survivors, 30 patients. The survivors group included 58 patients and 30 patients who were not survivors. The mortality rate was determined at 34.09%. No significant differences were found between the groups in terms of gender and age. The averages of the APACHE II scores were higher in the non-survivor group (p <0.001) and no difference was determined for the median SOFA score (p >0.05). Laboratory results indicated similar levels of LDL, HDL and TG in both groups (p >0.05). All demographics and laboratory data can be found in Table 1. Univariate analysis showed that APACHE II and SOFA scores may be factors that affect the adverse clinical outcome of sepsis (Table 2). Compared to surviving patients, non-surviving patients also showed higher APACHE II and SOFA scores. Multivariate analysis showed that APACHE II (OR, 1.178; 95% CI, 1.063–1.306; p = 0.002) levels were found to be independent predictors of adverse clinical outcomes of sepsis (Table 2). Higher APACHE II levels were predictive of adverse clinical outcomes. LDL, HDL and TG levels were not a predictor of adverse clinical outcomes.

In our study, no significant correlation was found between lipid profile and mortality in geriatric patients with sepsis. We detected the APACHE-2 score as an independent risk factor in in geriatric patients with sepsis.

In the study of Tanaka et al. in 2017; It was stated that HDL was significantly lower in the sepsis group compared to the tarvama group, but LDL and TG did not show differences between the groups. However, in the subgroup analysis of the study, no relationship was found between lipid profile and mortality in patients with sepsis [9].

In the study of Nabavi et al. in 2020; found that the decrease in plasma lipid values during the follow-up of the patients in the intensive care unit was associated with mortality. However, they found that the baseline lipid profile of the patients during their admission to the intensive care unit was not associated with mortality [10].

Table 1: Basic Patient Characteristics as A Function of Mortality Status

Abbreviations: APACHE II score: Acute Physiology and Chronic Health Evaluation II score, SOFA: Sequential Organ Failure Assessment, TG: Triglyceride, LDL: Low-Density Lipoprotein, HDL: High-Density Lipoprotein.

Table 2: Predictors of Mortality Through Univariate and Multivariate Logistics Regression Analyses

Abbreviations: APACHE II score: Acute Physiology and Chronic Health Evaluation II score, SOFA: Sequential Organ Failure Assessment, TG: Triglyceride, LDL: Low-Density Lipoprotein, HDL: High-Density Lipoprotein, OR: Odds Ratio, CI: Confidence Interval.

In the study of Maile et al. in 2020; high LDL and TG levels were found to be associated with lower mortality. In addition, in this study, it was found that statin using before sepsis was not associated with mortality [11].

In the study of Delirrad and et al. in 2019; TG levels were found to be significantly higher in the surviving patients with sepsis group compared to the non-survivors’ patients with sepsis group. However, no significant difference was found between the groups in terms of mortality total cholesterol, LDL and, HDL [12].

In a study published by Guirgis et al. in 2016, it was determined that low LDL levels constitute a significant risk factor for the long-term risks of sepsis (including mortality). However, they did not find a significant relationship between HDL and the long-term risks of sepsis (including mortality) [13].

Other studies in the literature have demonstrated that low cholesterol levels are a risk factor for sepsis. Also shown that lipid levels change rapidly in early sepsis and can predict the results [14-16].

When we look at the literature, there is still uncertainty in determining the prognosis of sepsis patients with the lipid profile values measured during admission to the intensive care unit. In our study, we aimed to eliminate this ambiguity. In addition, we examined the relationship between the baseline lipid profile and mortality in the geriatric patients with sepsis group, which has never been studied before. In our study, we did not find statistically significant results between baseline lipid profile and mortality. We associated this situation primarily with the fact that we conducted a study in a patient group with a high risk of mortality. In addition, we did not record whether the patients in the study group used lipid-lowering drugs before and their fasting status. These conditions, which constitute the limitations of our study, may have led to similarity between groups. In addition, other limitations of our study; It is a single-center retrospective study and we did not evaluate lipid values by serial measurement.

Our study was in the geriatric patients with sepsis group; This is the first study to evaluate the relationship between baseline lipid profile and mortality. Our study will lead the future studies to be done in this patient group. However, there is a need for multicenter, prospective studies with large patient groups.

1. A. Rhodes et al. "Surviving sepsis campaign international guidelines for management of sepsis and septic shock 2016." Intensive Care Med., vol. 43, no. 3, 2017, pp. 304–377.

2. G.S. Martin et al. "The epidemiology of sepsis in the United States from 1979 through 2000."N. Engl. J. Med., vol. 348, no. 16, 2003, pp. 1546–1554.

3. K.M. Ho et al. "A comparison of admission and worst 24-hour acute physiology and chronic health evaluation II scores in predicting hospital mortality a retrospective cohort study." Crit. Care, vol. 10, no. 1, 2005, pp. 1–8.

4. J.L. Vincent et al. "Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units results of a multicenter prospective study." Crit. Care Med., vol. 26, no. 11, 1998, pp. 1793–1800.

5. Q. Yang et al. "Predicted 10-year risk of developing cardiovascular disease at the state level in the US." Am. J. Prev. Med., vol. 48, no. 1, 2015, pp. 58–69.

6. B.A. Ference et al. "Low-density lipoproteins cause atherosclerotic cardiovascular disease 1 evidence from genetic epidemiologic and clinical studies." Eur. Heart J., vol. 38, no. 32, 2017, pp. 2459–2472.

7. H. Ghandehari et al. "Prevalence and extent of dyslipidemia and recommended lipid levels in US adults with and without cardiovascular comorbidities." Am. Heart J., vol. 156, no. 1, 2008, pp. 112–119.

8. M. Singer et al. "The third international consensus definitions for sepsis and septic shock (Sepsis-3)." JAMA, vol. 315, no. 8, 2016, pp. 801–810.

9. S. Tanaka et al. "Low HDL levels in sepsis versus trauma patients in intensive care unit." Ann. Intensive Care, vol. 7, no. 1, 2017, pp. 1–8.

10. A. Nabavi et al. "Changes in plasma lipid and in-hospital deaths in patients with sepsis." Med. J. Islam. Repub. Iran, vol. 34, no. –, 2020, p. 45.

11. M.D. Maile et al. "Impact of the pre-illness lipid profile on sepsis mortality." J. Crit. Care, vol. 57, no. –, 2020, pp. 197–202.

12. M. Delirrad et al. "Relationship between lipid profile and sepsis outcome in intensive care unit." Arch. Clin. Infect. Dis., vol. 15, no. 2, 2020.

13. F.W. Guirgis et al. "Cholesterol levels and long-term rates of community-acquired sepsis." Crit. Care, vol. 20, no. 1, 2016, pp. 1–12.

14. L. Lagrost et al. "Low preoperative cholesterol level is a risk factor of sepsis and poor clinical outcome in patients undergoing cardiac surgery with cardiopulmonary bypass."Crit. Care Med., vol. 42, no. 5, 2014, pp. 1065–1073.

15. S.H. Lee et al. "Prognostic implications of serum lipid metabolism over time during sepsis." Biomed. Res. Int., vol. 2015, no. –, 2015.

16. J.Y. Chien et al. "Low serum level of high-density lipoprotein cholesterol is a poor prognostic factor for severe sepsis." Crit. Care Med., vol. 33, no. 8, 2005, pp. 1688–1693.