Differential and cumulative impact of metabolic syndrome traits on cardiovascular, renal, and mortality outcomes in cancer patients.

Abstract

11060 Background: Metabolic syndrome (MetS) is a known risk factor for developing at least 13 cancer types and adverse outcomes. However, the effects of MetS on their differential and cumulative impact on cardiovascular, renal, and mortality outcomes in cancer patients remains uncertain. We aimed to determine whether MetS components increase cancer patients' risk of adverse cardiorenal and all-cause mortality. Methods: This large retrospective cohort study used the TriNetX database between 2013 to 2024. Adults (>18 years) with new cancer diagnoses and ≥1 MetS trait (obesity, insulin resistance(IR), hypertension (HT), or dyslipidemia (DLD)) were compared with matched controls without MetS. We performed 1:1 propensity score matching to adjust for confounding factors (demographics, comorbidities, cancer type, and medications). The primary outcomes were new adverse cardiovascular events like heart failure (HF), major adverse cardiovascular events (MACE), and cerebrovascular events (CVE). The secondary outcomes were end-stage renal diseases (ESRD), the need for dialysis, and all-cause mortality. We conducted sensitivity analyses to assess the robustness of the findings. Hazard ratios(HR) were calculated using Cox regression models stratified by MetS traits. Results: In total, 204,297 patients were identified (median age 54 years) with a median follow-up of 7.8 years. Patients with ≥1 MetS trait had significantly increased risks of adverse cardiorenal events. HR for HF was 1.76; this risk increased to 2.54 with ≥3 MetS traits. The risk of MACE was HR of 2.34 in those with ≥1 trait and HR of 2.47 in those with 4 traits. CVE had an HR of 1.56, increasing to 2.38 with ≥3 traits. For secondary outcomes, the risk of ESRD was HR of 1.76 in patients with ≥1 MetS trait, rising to HR of 2.29 in those with ≥3 traits. The need for dialysis was significantly elevated (HR 1.86), and all-cause mortality was HR of 2.15 in patients with ≥1 trait, increasing to 3.10 with 4 traits. Stratified analyses revealed obesity increased HF risk (HR 1.58) and mortality (HR 1.75). IR was linked to higher risks of MACE (HR 1.88) and ESRD (HR 2.59). HT increased the risk of CVE (HR 2.16) and dialysis (HR 2.11). DLD moderately elevated the risk of IHD (HR 1.47) and mortality (HR 1.59). Sensitivity analyses confirmed these findings across cancer types and treatments. A cumulative relationship was observed, with the number of MetS traits correlating to higher risks of outcomes. Conclusions: Our study showed a differential effect of MetS components on cardiovascular, renal, and all-cause mortality outcomes in cancer patients, with a cumulative impact of multiple MetS on overall risk. Early intervention targeting MetS traits may reduce these risks and improve outcomes. Comprehensive metabolic management should be integrated into oncology care to mitigate these risks and improve patient outcomes.