Prognostic value of soluble ST2, high-sensitivity cardiac troponin, and NT-proBNP in type 2 diabetes: a 15-year retrospective study

Background: Patients with type 2 diabetes (T2DM) present an increased risk of cardiovascular (CV) disease and excess CV-related mortality. Beyond the established role of brain natriuretic peptide (BNP) and cardiac troponins (cTn), other non-cardiac-specific biomarkers are emerging as predictors of CV outcomes in T2DM. Methods: Serum levels of soluble suppression of tumorigenesis 2 (sST2), high-sensitivity (hs)-cTnI, and N-terminal (NT)-proBNP were assessed in 568 patients with T2DM and 115 healthy controls (CTR). Their association with all-cause mortality and the development of diabetic complications was tested in T2DM patients over a median follow-up of 16.8 years using Cox models and logistic regressions. Results: sST2 followed an increasing trend from CTR to uncomplicated T2DM patients (T2DM-NC) to patients with at least one complication (T2DM-C), while hs-cTnI was significantly higher in T2DM-C compared to CTR but not to T2DM-NC. A graded association was found between sST2 (HR 2.76 [95% CI 1.20-6.33] for ≥ 32.0 ng/mL and 2.00 [1.02-3.94] for 16.5-32.0 ng/mL compared to < 16.5 ng/mL, C-statistic = 0.729), NT-proBNP (HR 2.04 [1.90-4.55] for ≥ 337 ng/L and 1.48 [1.05-2.10] for 89-337 ng/L compared to < 89 ng/L, C-statistic = 0.741), and 15-year mortality in T2DM, whereas increased mortality was observed in patients with hs-cTnI ≥ 7.8 ng/L (HR 1.63 [1.01-2.62]). A 'cardiac score' based on the combination of sST2, hs-cTnI, and NT-proBNP was significantly associated with all-cause mortality (HR 1.35 [1.19-1.53], C-statistic = 0.739) and development of CV events. Conclusions: sST2, hs-cTnI, and NT-proBNP are associated with 15-year mortality and onset of CV events in T2DM. The long-term prognostic value of sST2 and its ability to track variables related to insulin resistance and associated metabolic disorders support its implementation into routine clinical practice

91 Circulating lipid profile as a prognostic factor in patients with advanced solid tumors treated with immune checkpoint inhibitors

Background Components of lipid profile seem to impact differently on phenotype and activity of immune cells in cancer.1,2 Their prognostic role in solid cancer patients treated with immune checkpoint inhibitors (ICIs) is still matter of debate. Methods We retrospectively collected baseline clinicopathological characteristics including circulating lipid profile [total cholesterol (TC), triglycerides (TGs), low-density lipoproteins (LDL), high-density lipoproteins (HDL)] of consecutive solid cancer patients treated with ICIs and we investigated their impact on clinical outcomes. Cut-off values showing alteration of plasma lipid profile were ≥200 mg/dl for TC, ≥170 mg/dl for TGs, ≥130 mg/dl for LDL, <40 mg/dl for HDL in males, <45 mg/dl for HDL in females. Results Among 432 patients enrolled, 67% (N=289) were men, 61% (N=266) were diagnosed with advanced non-small cell lung cancer and 86.6% (N=374) of patients were treated with ICIs as monotherapy. Patients’ circulating lipid assessments were described in tables (tables 1–3). At a median follow-up of 46 months, patients with TC≥200 mg/dl showed an improved, although not significant, progression free survival (PFS) (6.61 versus 4.67 months, p=0.4) and longer overall survival (OS) (19.4 versus 10.8 months, p=0.02) compared to those with TC<200 mg/dl. Conversely, patients with TGs≥170 mg/dl showed a shorter PFS (2.8 versus 5.07 months, p=0.006) and OS (5.92 versus 12.99 months, p<0.001) compared to those with TGs<170 mg/dl. Then, we combined TC and TGs in a LIPID-score that identified three subgroups: good risk (GR) (TC≥200 mg/dl and TGs<170 mg/dl), intermediate risk (IR) (TC<200 mg/dl and TGs<170 mg/dl or TC≥200 mg/dl and TGs≥170 mg/dl) and poor risk (PR) (TC<200 mg/dl and TGs≥170 mg/dl). The median PFS of GR, IR and PR groups was 7.76, 4.18 and 2.40 months, respectively (p<0.001). Moreover, median OS of GR, IR and PR was 20.36, 11.18 and 4.14 months, respectively (p<0.001) (figure 1). At multivariate analyses, after adjusting for baseline performance status, histology, treatment line, sex, statin use, number of metastatic sites and body mass index, the impact of LIPID score remained significant for both PFS and OS (table 4). Looking at TC components, HDL and LDL, a significant association was detected only for HDL and OS, with patients characterized by higher HDL levels showing longer OS (15.3 vs 10.1 months, p=0.02). Conclusions LIPID score seems to strongly define subgroups of patients treated with ICIs with different prognosis. Further mechanistic insights are needed to clarify the prognostic and predictive role of lipid profile components in patients treated with ICIs

Prognostic Impact of Blood Lipid Profile in Patients With Advanced Solid Tumors Treated With Immune Checkpoint Inhibitors: A Multicenter Cohort Study

Background: Specific components of lipid profile seem to differently impact on immune activity against cancer and unraveling their prognostic role in patients with solid cancer treated with immune checkpoint inhibitors (ICIs) is needed. Materials and methods: We retrospectively collected baseline clinicopathological characteristics including circulating lipid profile (total cholesterol [TC], triglycerides [TG], low-density lipoproteins [LDL], high-density lipoproteins [HDL]) of patients with consecutive solid cancer treated with ICIs, and we investigated their role in predicting clinical outcomes. Results: At a median follow-up of 32.9 months, among 430 enrolled patients, those with TC ≥ 200 mg/dl showed longer median progression-free survival (mPFS; 6.6 vs. 4.7 months, P = .4), although not reaching statistical significance, and significantly longer median overall survival (mOS; 19.4 vs. 10.8 months, P = .02) compared to those with TC < 200 mg/dl. Conversely, patients with TG ≥150 mg/dl displayed shorter PFS (3.4 vs. 5.1 months, P = .02) and OS (7.1 vs. 12.9 months, P = .009) compared to those with TG <150 mg/dl. TC and TG were then combined in a "LIPID score" identifying three subgroups: good-risk (GR) (TC ≥200 mg/dl and TG <150 mg/dl), intermediate-risk (IR) (TC <200 mg/dl and TG <150 mg/dl or TC ≥200 mg/dl and TG ≥150 mg/dl) and poor-risk (PR) (TC <200 mg/dl and TG ≥150 mg/dl). The mPFS of GR, IR, and PR groups was 7.8, 4.3, and 2.5 months, respectively (P = .005); mOS of GR, IR, and PR was 20.4, 12.4, and 5.3 months, respectively (P < .001). At multivariable analysis, the PR profile represented an independent poor prognostic factor for both PFS and OS. Conclusions: We developed a lipid score that defined subgroups of patients with cancer who differently benefit from ICIs. Further mechanistic insights are warranted to clarify the prognostic and predictive role of lipid profile components in patients treated with ICIs