Hyperlipidemia and Comprehensive Vascular Events (CVEs) - a Novel Outcome Measure for Peripheral Arterial Disease

Hyperlipidemia is a known risk factor for atherosclerosis. However, the impact of this comorbidity on the outcomes of patients with peripheral arterial disease (PAD) undergoing lower extremity revascularization (LER) is unknown. This study examines the incidence of major adverse cardiovascular (MACE) and limb (MALE) events after LER in patients with and without hyperlipidemia. A new combined outcome measure to assess overall vascular events in patients with PAD is introduced. A retrospective review of patients undergoing LER for PAD in a tertiary care center was conducted. Patients were divided into two groups based on the presence or absence of a recorded hyperlipidemia diagnosis at the time of initial LER. Characteristics and outcomes of patients in the two groups were compared. Comprehensive vascular events (CVEs) were defined as a composite outcome of cardiovascular (non-fatal myocardial infarction, cardiac revascularization, and stroke) and limb (ipsilateral reintervention or major amputation) events (CVE = MACE + MALE). A total of 1948 patients underwent LER, of which 1497 (76.8%) had hyperlipidemia. Patients with hyperlipidemia were more likely to be White with higher body mass index (BMI) and had significantly higher prevalence of hypertension, smoking history, coronary artery disease, stroke, and prior LER. On the other hand, patients without hyperlipidemia were more likely to have renal disease but less likely to be on optimal statin and antiplatelet therapy. Patients with hyperlipidemia were more likely to undergo LER for claudication using endovascular procedures (Table). There was no difference in perioperative complications. On follow-up, patients with hyperlipidemia had higher myocardial infarction and coronary revascularization but lower major amputation and mortality compared to patients without hyperlipidemia. Kaplan-Meier analysis showed patients with hyperlipidemia had longer survival time to first CVE or all-cause death (P = .003). (Fig) After adjusting for comorbidities, indication, and baseline statin and antithrombotic use, regression analysis demonstrated that hyperlipidemia was independently associated with higher MALE-free survival (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.05-1.39) and CVE-free survival (HR, 1.17; 95% CI, 1.02-1.34) but not MACE-free survival (HR, 1.00; 95% CI, 0.85-1.17). Conversely, chronic renal insufficiency (HR, 1.25; 95% CI, 1.06- 1.46) and end-stage renal disease (ESRD) (HR, 1.5; 95% CI, 1.21-1.87) were independently associated with increased CVE or death. Hyperlipidemia is not associated with worse outcomes in patients with advanced PAD, but renal disease and suboptimal medical therapy may be drivers of adverse events. CVE is a useful measure to assess the impact of various factors and therapies on overall vascular events in patients with PAD.TablePatient characteristics and outcomesHLDn = 1497 (76.8)No HLDn = 451 (23.2)P valueBaseline characteristics Age, years70 (11)69 (13).106 Male953 (64)277 (61).387 Race.001White1170 (79)315 (71)Black191 (13)87 (20)Other126 (8.5)44 (9.9) BMI, kg/m228 (6)27 (8)<.001Comorbidities Coronary artery disease895 (60)154 (34)<.001 Hypertension1409 (94)350 (78)<.001 Congestive heart failure261 (18)66 (15).149 Diabetes877 (59)242 (54).056 Smoking history1220 (82)341 (76).004Chronic kidney disease stage<.0011315 (24)131 (34)2558 (42)136 (35)3395 (30)109 (28)445 (3.4)9 (2.3)56 (0.5)6 (1.5) End-stage renal disease110 (7.5)47 (11).044 Stroke231 (15)47 (10).008 Prior endovascular procedure322 (22)74 (17).018 Prior open procedure172 (12)46 (10).451Baseline medications Statins1226 (82)233 (52)<.001 ASA1155 (78)294 (66)<.001 P2Y12 Inhibitors508 (34)97 (22)<.001 Anticoagulants279 (19)83 (18).911Procedural characteristics Indication<.001Claudication825 (55)152 (34)CLTI662 (45)298 (66) Surgical approach.041Open surgery139 (9.3)59 (13)Endovascular1325 (89)379 (84)Hybrid33 (2.2)13 (2.9)Perioperative outcomes (30-day) Mortality12 (0.8)5 (1.1).565 Thrombosis15 (1.0)4 (0.9)1.000 Myocardial infarction17 (1.1)5 (1.1).968 Stroke4 (0.3)2 (0.5).626 Major amputation9 (0.6)7 (1.6).068Long-term outcomes Follow-up time, years4.45 (2.80)3.98 (2.83).001 MACE500 (34)111 (25).001Myocardial infarction334 (23)76 (17).017Percutaneous coronary revascularization167 (11)27 (6.1).002 Coronary artery bypass graft83 (5.6)8 (1.8).001Stroke101 (6.8)21 (4.7).119 MALE709 (48)235 (54).035Reintervention677 (45)204 (45).997Major amputation105 (7.2)64 (15)<.001 CVE = MACE + MALE935 (64)278 (64).833 Mortality585 (39)201 (45).038BMI, Body mass index; CVE, comprehensive vascular event; HLD, hyperlipidemia; MACE, major adverse cardiovascular events; MALE, major adverse limb events.Data are presented as number (%) or mean (standard deviation).Boldface P values indicate statistical significance. Open table in a new tab