Prognostic value of lipoprotein(a) for cardiovascular events after lower limb revascularization in diabetic patients with chronic limb-threatening ischemia
Abstract Background Chronic limb-threatening ischemia (CLTI) presents a major clinical challenge in patients with Type 2 Diabetes Mellitus (T2DM), requiring lower extremity revascularization (LER) to mitigate adverse cardiovascular and limb outcomes. Lipoprotein(a) (Lp(a)) has been implicated in car...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-07-01
|
| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12933-025-02833-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849767549307191296 |
|---|---|
| author | Federico Biscetti Maria Margherita Rando Maria Anna Nicolazzi Flavia Angelini Roberto Iezzi Luis H. Eraso Paul J. Dimuzio Dario Pitocco Massimo Massetti Antonio Gasbarrini Andrea Flex |
| author_facet | Federico Biscetti Maria Margherita Rando Maria Anna Nicolazzi Flavia Angelini Roberto Iezzi Luis H. Eraso Paul J. Dimuzio Dario Pitocco Massimo Massetti Antonio Gasbarrini Andrea Flex |
| author_sort | Federico Biscetti |
| collection | DOAJ |
| description | Abstract Background Chronic limb-threatening ischemia (CLTI) presents a major clinical challenge in patients with Type 2 Diabetes Mellitus (T2DM), requiring lower extremity revascularization (LER) to mitigate adverse cardiovascular and limb outcomes. Lipoprotein(a) (Lp(a)) has been implicated in cardiovascular risk, but its role in patients with T2DM and CLTI undergoing revascularization remains unclear. Thus, this study aimed to investigate the prognostic value of Lp(a) levels in diabetic CLTI patients for major adverse cardiovascular events (MACE), major adverse limb events (MALE), or both after LER. Methods In this prospective cohort study of 158 individuals with T2DM and CLTI undergoing LER, baseline clinical data were collected, including Lp(a) levels. Patients were followed for occurrence of MACE, MALE, or both over a 12-month period. Results During follow-up, 74 patients (46.8%) experienced events (MACE, MALE, or both). Patients with events had significantly higher median Lp(a) levels than those without (48.0 vs. 8.1 mg/dL, p < 0.01). Lp(a) was independently associated with adverse events (HR 1.07, 95% CI 1.04–1.10; p < 0.01). In multivariable analysis, elevated Lp(a) was independently associated with both MACE (HR 1.08, 95% CI 1.03–1.13; p < 0.01) and MALE (HR 1.05, 95% CI 1.02–1.07; p < 0.01). An empirical Lp(a) cutoff of 29.6 mg/dL conferred a 3.8-fold increased risk of events (p < 0.01). Kaplan–Meier survival analysis further confirmed a significantly higher cumulative incidence of events in patients with Lp(a) levels above cutoff (p < 0.01). ROC curve comparison analysis showed that the inclusion of Lp(a) significantly improved the predictive performance of the base clinical model (AUC from 0.74 to 0.98, p < 0.01 for composite outcome; from 0.81 to 0.89, p = 0.03 for MACE; and from 0.78 to 0.92, p < 0.01for MALE). Conclusions This study demonstrated that Lp(a) is a strong independent predictor of both cardiovascular and limb events in patients with T2DM undergoing LER for CLTI. These findings support the potential role of Lp(a) as a marker of residual risk in this high-risk population and suggest its utility in risk stratification. |
| format | Article |
| id | doaj-art-8d087ebbf4c1468b9cdb9ac92cd29e21 |
| institution | DOAJ |
| issn | 1475-2840 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj-art-8d087ebbf4c1468b9cdb9ac92cd29e212025-08-20T03:04:10ZengBMCCardiovascular Diabetology1475-28402025-07-0124111610.1186/s12933-025-02833-2Prognostic value of lipoprotein(a) for cardiovascular events after lower limb revascularization in diabetic patients with chronic limb-threatening ischemiaFederico Biscetti0Maria Margherita Rando1Maria Anna Nicolazzi2Flavia Angelini3Roberto Iezzi4Luis H. Eraso5Paul J. Dimuzio6Dario Pitocco7Massimo Massetti8Antonio Gasbarrini9Andrea Flex10Cardiovascular Internal Medicine Unit, Fondazione Policlinico Universitario A. Gemelli IRCCSCardiovascular Internal Medicine Unit, Fondazione Policlinico Universitario A. Gemelli IRCCSCardiovascular Internal Medicine Unit, Fondazione Policlinico Universitario A. Gemelli IRCCSUniversità Cattolica del Sacro CuoreUniversità Cattolica del Sacro CuoreDivision of Vascular and Endovascular Surgery, Thomas Jefferson UniversityDivision of Vascular and Endovascular Surgery, Thomas Jefferson UniversityUniversità Cattolica del Sacro CuoreUniversità Cattolica del Sacro CuoreUniversità Cattolica del Sacro CuoreCardiovascular Internal Medicine Unit, Fondazione Policlinico Universitario A. Gemelli IRCCSAbstract Background Chronic limb-threatening ischemia (CLTI) presents a major clinical challenge in patients with Type 2 Diabetes Mellitus (T2DM), requiring lower extremity revascularization (LER) to mitigate adverse cardiovascular and limb outcomes. Lipoprotein(a) (Lp(a)) has been implicated in cardiovascular risk, but its role in patients with T2DM and CLTI undergoing revascularization remains unclear. Thus, this study aimed to investigate the prognostic value of Lp(a) levels in diabetic CLTI patients for major adverse cardiovascular events (MACE), major adverse limb events (MALE), or both after LER. Methods In this prospective cohort study of 158 individuals with T2DM and CLTI undergoing LER, baseline clinical data were collected, including Lp(a) levels. Patients were followed for occurrence of MACE, MALE, or both over a 12-month period. Results During follow-up, 74 patients (46.8%) experienced events (MACE, MALE, or both). Patients with events had significantly higher median Lp(a) levels than those without (48.0 vs. 8.1 mg/dL, p < 0.01). Lp(a) was independently associated with adverse events (HR 1.07, 95% CI 1.04–1.10; p < 0.01). In multivariable analysis, elevated Lp(a) was independently associated with both MACE (HR 1.08, 95% CI 1.03–1.13; p < 0.01) and MALE (HR 1.05, 95% CI 1.02–1.07; p < 0.01). An empirical Lp(a) cutoff of 29.6 mg/dL conferred a 3.8-fold increased risk of events (p < 0.01). Kaplan–Meier survival analysis further confirmed a significantly higher cumulative incidence of events in patients with Lp(a) levels above cutoff (p < 0.01). ROC curve comparison analysis showed that the inclusion of Lp(a) significantly improved the predictive performance of the base clinical model (AUC from 0.74 to 0.98, p < 0.01 for composite outcome; from 0.81 to 0.89, p = 0.03 for MACE; and from 0.78 to 0.92, p < 0.01for MALE). Conclusions This study demonstrated that Lp(a) is a strong independent predictor of both cardiovascular and limb events in patients with T2DM undergoing LER for CLTI. These findings support the potential role of Lp(a) as a marker of residual risk in this high-risk population and suggest its utility in risk stratification.https://doi.org/10.1186/s12933-025-02833-2Peripheral artery disease (PAD)Lipoprotein(a) (Lp(a))Major adverse cardiovascular events (MACE)Major adverse limb events (MALE) |
| spellingShingle | Federico Biscetti Maria Margherita Rando Maria Anna Nicolazzi Flavia Angelini Roberto Iezzi Luis H. Eraso Paul J. Dimuzio Dario Pitocco Massimo Massetti Antonio Gasbarrini Andrea Flex Prognostic value of lipoprotein(a) for cardiovascular events after lower limb revascularization in diabetic patients with chronic limb-threatening ischemia Cardiovascular Diabetology Peripheral artery disease (PAD) Lipoprotein(a) (Lp(a)) Major adverse cardiovascular events (MACE) Major adverse limb events (MALE) |
| title | Prognostic value of lipoprotein(a) for cardiovascular events after lower limb revascularization in diabetic patients with chronic limb-threatening ischemia |
| title_full | Prognostic value of lipoprotein(a) for cardiovascular events after lower limb revascularization in diabetic patients with chronic limb-threatening ischemia |
| title_fullStr | Prognostic value of lipoprotein(a) for cardiovascular events after lower limb revascularization in diabetic patients with chronic limb-threatening ischemia |
| title_full_unstemmed | Prognostic value of lipoprotein(a) for cardiovascular events after lower limb revascularization in diabetic patients with chronic limb-threatening ischemia |
| title_short | Prognostic value of lipoprotein(a) for cardiovascular events after lower limb revascularization in diabetic patients with chronic limb-threatening ischemia |
| title_sort | prognostic value of lipoprotein a for cardiovascular events after lower limb revascularization in diabetic patients with chronic limb threatening ischemia |
| topic | Peripheral artery disease (PAD) Lipoprotein(a) (Lp(a)) Major adverse cardiovascular events (MACE) Major adverse limb events (MALE) |
| url | https://doi.org/10.1186/s12933-025-02833-2 |
| work_keys_str_mv | AT federicobiscetti prognosticvalueoflipoproteinaforcardiovasculareventsafterlowerlimbrevascularizationindiabeticpatientswithchroniclimbthreateningischemia AT mariamargheritarando prognosticvalueoflipoproteinaforcardiovasculareventsafterlowerlimbrevascularizationindiabeticpatientswithchroniclimbthreateningischemia AT mariaannanicolazzi prognosticvalueoflipoproteinaforcardiovasculareventsafterlowerlimbrevascularizationindiabeticpatientswithchroniclimbthreateningischemia AT flaviaangelini prognosticvalueoflipoproteinaforcardiovasculareventsafterlowerlimbrevascularizationindiabeticpatientswithchroniclimbthreateningischemia AT robertoiezzi prognosticvalueoflipoproteinaforcardiovasculareventsafterlowerlimbrevascularizationindiabeticpatientswithchroniclimbthreateningischemia AT luisheraso prognosticvalueoflipoproteinaforcardiovasculareventsafterlowerlimbrevascularizationindiabeticpatientswithchroniclimbthreateningischemia AT pauljdimuzio prognosticvalueoflipoproteinaforcardiovasculareventsafterlowerlimbrevascularizationindiabeticpatientswithchroniclimbthreateningischemia AT dariopitocco prognosticvalueoflipoproteinaforcardiovasculareventsafterlowerlimbrevascularizationindiabeticpatientswithchroniclimbthreateningischemia AT massimomassetti prognosticvalueoflipoproteinaforcardiovasculareventsafterlowerlimbrevascularizationindiabeticpatientswithchroniclimbthreateningischemia AT antoniogasbarrini prognosticvalueoflipoproteinaforcardiovasculareventsafterlowerlimbrevascularizationindiabeticpatientswithchroniclimbthreateningischemia AT andreaflex prognosticvalueoflipoproteinaforcardiovasculareventsafterlowerlimbrevascularizationindiabeticpatientswithchroniclimbthreateningischemia |