To determine the relationship between non-high-density lipoprotein cholesterol (non-HDL-c), systolic blood pressure (SBP) and smoking and the risk of major adverse limb events (MALE) and the combination with major adverse cardiovascular events (MALE/MACE) in patients with symptomatic vascular disease.Patients with symptomatic vascular disease from the Utrecht Cardiovascular Cohort - Secondary Manifestations of ARTerial disease (1996-2017) study were included. The effects of non-HDL-c, SBP and smoking on the risk of MALE were analysed with Cox proportional hazard models stratified for presence of peripheral artery disease (PAD). MALE was defined as major amputation, peripheral revascularisation or thrombolysis in the lower limb.In 8139 patients (median follow-up 7.8 years, IQR 4.0-11.8), 577 MALE (8.7 per 1000 person-years) and 1933 MALE/MACE were observed (29.1 per 1000 person-years). In patients with PAD there was no relation between non-HDL-c and MALE, and in patients with coronary artery disease (CAD), cerebrovascular disease (CVD) or abdominal aortic aneurysm (AAA) the risk of MALE was higher per 1mmol/L non-HDL-c (HR 1.14, 95%CI 1.01 to 1.29). Per 10mm Hg SBP, the risk of MALE was higher in patients with PAD (HR 1.06, 95%CI 1.01 to 1.12) and in patients with CVD/CAD/AAA (HR 1.15, 95%CI 1.08 to 1.22). The risk of MALE was higher in smokers with PAD (HR 1.45, 95%CI 0.97 to 2.14) and CAD/CVD/AAA (HR 7.08, 95%CI 3.99 to 12.57).The risk of MALE and MALE/MACE in patients with symptomatic vascular disease differs according to vascular disease location and is associated with non-HDL-c, SBP and smoking. These findings confirm the importance of MALE as an outcome and underline the importance of risk factor management in patients with vascular disease.
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