Jonathan Golledge

Journal of atherosclerosis and thrombosis • March 05, 2025

Jonathan Golledge, Alkira Venn, Anthony Leicht, Nicola Burton, Belinda Parmenter, Joseph Moxon

Objective: This post-hoc analysis from the Behavioural Intervention by allied health professionals to promote Physical activity (BIP) trial examined the relationship between depression and step count and walking capacity over two years in people with peripheral artery disease (PAD). Methods: BIP included participants with walking impairment due to PAD followed up at 4, 12 and 24 months to measure step count over 7 days using an accelerometer and six-minute walking distance. The relationships between depression at entry with step count and walking distance during follow-up were assessed using linear mixed effects models. Results: At entry, 29 (14.5%) of the 200 participants had depression being treated with anti-depressant medication. Participants diagnosed with depression were more likely to be female (13 of 29, 44.8%) than those not diagnosed with depression (43 of 171, 25.1%). Over 24 months follow-up, daily step count progressively decreased in participants with depression (mean [SD] 4406 (2266) at entry to 3888 (2555) at 24 months) as compared to no change in participants without depression (mean (SD) 5271 (2526) at entry compared to 5120 (2446) at 24 months), inter-group difference p = 0.010. No significant difference in change in six-minute walking distance over 2 years was found between participants with and those without depression. Conclusions: Depression is associated with greater decline in self-regulated walking in patients with PAD. Effective treatments for depression are needed which help promote physical activity in people with PAD.

Arteriosclerosis, Thrombosis, And Vascular Biology • August 07, 2025

Matthew Allison, Janet Powell, Jonathan Golledge

Atherothrombotic occlusion and narrowing of the arteries supplying blood to the legs, usually referred to as peripheral artery disease, affects 6% of adults and is associated with impaired quality of life and increased risk of major adverse events including death. Peripheral artery disease has been relatively understudied and has not been subject to the same scrutiny and investigation that characterizes coronary artery disease. Importantly, there are subtle differences between peripheral and coronary artery disease with respect to traditional risk factors, and there may be marked differences in nontraditional risk factors. Here, we provide a brief description of the population burden, pathophysiology, and traditional risk factors for peripheral artery disease, which is intended as the introduction to a series of reviews focusing on nontraditional risk factors for this disorder. We highlight the planned reviews in the series and how these may act as an important impetus to address the unmet need of improving outcomes in people with peripheral artery disease.

Current Opinion In Lipidology • May 21, 2025

Shivshankar Thanigaimani, Maarisha Kumar, Jonathan Golledge

Objective: Peripheral artery disease (PAD) is a major cause of global health burden, including amputation and impaired quality of life. This review examines the evidence implicating lipoprotein(a) [Lp(a)] in PAD, which is timely as novel therapies lowering Lp(a) are currently being tested in several clinical trials. Results: Human observational studies demonstrate strong associations between elevated Lp(a) levels and increased risk of PAD incidence, severity of chronic limb-threatening ischemia, and major adverse limb events. Emerging therapies including small interfering RNA, antisense oligonucleotides, proprotein convertase subtilisin-kexin type 9 inhibitors and lipoprotein apheresis demonstrate significant Lp(a)-lowering effects. However, whether these treatments benefit patients with PAD is currently unknown. Conclusions: Lp(a) may be involved in PAD pathogenesis. Lp(a)-lowering therapies may significantly reduce PAD-related events and improve outcomes. Future studies are needed to test Lp(a)-lowering therapies in people with PAD and to explore how the association of Lp(a) varies in different sexes and ethnicities and understand mechanisms by which Lp(a) may contribute to limb ischemia.

BMJ Open • January 25, 2025

Christopher Askew, Mark Windsor, Krist Feka, Fraser Russell, Mia Schaumberg, Meegan Walker, Bruce Neal, Adrian Esterman, Lucas Litewka, Jonathan Golledge

Background: Patients with peripheral artery disease (PAD) can experience intermittent claudication, which limits walking capacity and the ability to undertake daily activities. While exercise therapy is an established way to improve walking capacity in people with PAD, it is not feasible in all patients. Neuromuscular electrical stimulation (NMES) provides a way to passively induce repeated muscle contractions and has been widely used as a therapy for chronic conditions that limit functional capacity. Preliminary trials in patients with PAD demonstrate that stimulation of the leg muscles using a footplate-NMES device can be performed without pain and may lead to significant gains in walking capacity. Studies, to date, have been small and have not been adequately controlled to account for any potential placebo effect. Therefore, the current trial will compare the effect of a 12-week programme of footplate-NMES with a placebo-control on walking capacity (6 min walking distance) and other secondary outcomes in patients with PAD. Methods: The Foot-PAD trial is a double-blinded, randomised placebo-controlled trial to determine the effect of a 12-week home-based programme of footplate NMES on walking capacity in people with PAD. This is a single-centre trial with numerous recruitment locations. A total of 180 participants with stable PAD and intermittent claudication will be randomly assigned (1:1 ratio) to receive either footplate-NMES (intervention condition) or footplate-placebo (control condition) for two 30 min periods each day for 12 weeks. The footplate-NMES device will deliver stimulation sufficient to induce contraction of the leg muscles and repeated plantar and dorsiflexion at the ankles. The footplate-placebo device will deliver a momentary low-intensity transient stimulation that is insufficient to induce contraction of the leg muscles. Outcomes will be assessed at baseline (week 0), mid-intervention (week 6), postintervention (week 12) and 6 weeks after the completion of the intervention (week 18). The primary outcome is walking capacity at week 12, measured as maximum walking distance during the 6 min walk test. Secondary outcomes will include pain-free walking distance during the 6 min walk test; pain-free and maximum walking time during a graded treadmill walking test; disease-specific quality of life (Intermittent Claudication Questionnaire), self-reported walking impairment (Walking Impairment Questionnaire) and accelerometer-derived physical activity levels. Exploratory outcomes will include the Ankle-Brachial Index; leg vascular function; perception of device-use experience and symptom monitoring throughout the trial using the Claudication Symptom Instrument and a pain Visual Analogue Scale. Background: The Foot-PAD trial has received ethics approval from the Human Research Ethics Committees of Queensland Health Metro North Hospital and Health Service (78962) and the University of the Sunshine Coast (A21659). Regardless of the study outcomes, the study findings will be published in peer-reviewed scientific journals and presented at scientific meetings. Background: ACTRN12621001383853.

Journal Of Foot And Ankle Research • January 04, 2025

Mike Wu, Mallika Sinha, Chanika Alahakoon, Kristen Barratt, Shivshankar Thanigaimani, Jonathan Golledge

Background: The aim of this study was to systematically review the risk of falls in people with diabetes-related foot ulcers (DFU). Methods: A systematic search of Medline, Pubmed, Embase, Cochrane and CINAHL was undertaken to identify observational studies reporting falls and containing a group of people with a DFU and a control group with diabetes but no DFU. Risk of bias was assessed by a modified Newcastle-Ottawa Scale. Meta-analysis was performed using a random effects model. Results: Four studies involving 3643 participants with a DFU and 42,436 participants with diabetes but no DFU were included. A meta-analysis showed high heterogeneity between studies (I2 = 95%) and an increased risk of falls in people with DFU (risk ratio 2.25 and 95% CI 1.05-4.84). One study had a low risk of bias and three studies had a high risk of bias. Leave-one-out analyses showed that exclusion of the study with the largest effect on heterogeneity resulted in a risk ratio of 1.80 (95% CI 1.33-2.43 and I2 = 0%). Conclusions: Currently available evidence suggests people with a DFU have a higher risk of falls but most past studies have a high risk of bias. Further well-designed cohort studies are required.