Bruce C. Neal

JAMA cardiology • February 05, 2025

Xiong Ding, Xinyi Zhang, Liping Huang, Shangzhi Xiong, Zhifang Li, Yi Zhao, Bo Zhou, Xuejun Yin, Bingqing Xu, Yanfeng Wu, Bruce Neal, Maoyi Tian, Lijing Yan

The direct effect of consumption of salt substitutes on recurrent stroke and mortality among patients with stroke remains unclear. To evaluate the effects of salt substitutes vs regular salt on the incidence of recurrent stroke and mortality among patients with stroke. The Salt Substitute and Stroke Study (SSaSS), an open-label, cluster randomized clinical trial, was conducted in 600 northern Chinese villages (clusters). Patients who self-reported a hospital diagnosis of stroke were included in this prespecified subgroup analysis. Data were analyzed from November 2023 to August 2024. Participants were assigned to use either a salt substitute, consisting of 75% sodium chloride and 25% potassium chloride by mass, or regular salt. The primary outcome was recurrent stroke. After excluding 5746 persons without a baseline history of stroke, 15 249 patients with stroke (mean [SD] age, 64.1 [8.8] years; 6999 [45.9%] female; 8250 male [54.1%]) were included. Over a median (IQR) follow-up of 61.2 (60.9-61.6) months, the mean difference in systolic blood pressure was -2.05 mm Hg (95% CI, -3.03 to -1.08 mm Hg). A total of 2735 recurrent stroke events (691 fatal and 2044 nonfatal) and 3242 deaths were recorded. Recurrent stroke was significantly lower in the salt substitute vs regular salt group (rate ratio [RR], 0.86; 95% CI, 0.77-0.95; P = .005), with larger effects on hemorrhagic stroke (relative reduction, 30%; P = .002). Death rates were also significantly lower (RR, 0.88; 95% CI, 0.82-0.96; P = .003), with larger effects on stroke-related deaths (relative reduction 21%; P = .01). No significant difference was observed for hyperkalemia (RR, 1.01; 95% CI, 0.74-1.38; P = .96). Results of this cluster trial demonstrate that salt substitution was safe, along with reduced risks of stroke recurrence and death, which underscores large health gains from scaling up this low-cost intervention among patients with stroke. ClinicalTrials.gov Identifier: NCT02092090.

Heart, Lung & Circulation • April 14, 2025

Clara Chow, Jason Kovacic, Bruce Neal, Geoffrey Donnan, Alex Brown, Louise Maple Brown, Karen Carey, Richard Taggart, Pamu Kularathna, Sally Mcneill, Stephen Nicholls

Nutrition, Metabolism, And Cardiovascular Diseases : NMCD • February 23, 2025

Katrina Kissock, Clementina Okoro, Kathy Trieu, Nanna Ripiye, Anthony Orji, Mark Huffman, Bruce Neal, Dike Ojji

Objective: Excess sodium intake is associated with elevated blood pressure, a major risk factor for cardiovascular disease. Lowering sodium intake by switching regular salt for reduced-sodium salt may attenuate rises in blood pressure with age. We aimed to assess project feasibility in Nigeria before testing in a large-scale clinical trial. Results: We conducted an unblinded, non-randomised feasibility study in two rural Nigerian communities between March and May 2024. Participants (≥6 years) were recruited at the household level and provided with reduced-sodium salt (66 % KCl, 34 % NaCl) to replace all regular salt for cooking and seasoning over two months. Outcomes included recruitment rate, adherence and acceptability of the reduced-sodium salt, adherence to study procedures, and willingness to participate in a longer-term study. 41 households (148 participants) were recruited over five days. The median age of children, adolescents, and adults were 7, 11, and 35 years respectively, and 55 % were female. Nine participants (6 %) were lost to follow-up at 2-months (including two households), but 98 % of the scheduled follow-up visits were completed. At 2-months, 83 % of participants reported replacing all regular salt with reduced-sodium salt and most participants reported it was similar or better than regular salt for taste (94 %) and overall acceptability (93 %). All participants indicated willingness to engage in a 4-year study. Conclusions: It is feasible to conduct a large-scale clinical trial in Nigeria testing the effects of reduced-sodium salt compared to regular salt on the rise in blood pressure with age. Background: NCT05912426.

BMJ Open

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.

European Journal Of Epidemiology

Xiaoxia Li, Liping Huang, Bo Zhou, Zhifang Li, Jixin Sun, Yan Yu, Hongyi Song, Maoyi Tian, Xuejun Yin, Bruce Neal, Yuhong Zhang, Yangfeng Wu, Yi Zhao

The effect of a potassium-enriched salt substitute on cumulative blood pressure (BP) remains unclear. This study aimed to assess the long-term effects of a potassium-enriched salt substitute versus regular salt on cumulative and conventional measures of systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP). We analyzed data from the Salt Substitute and Stroke Study (SSaSS), a 5-year cluster randomized controlled trial in rural of China with 20,995 participants. The intervention used salt substitute; controls used regular salt. BP was measured for all participants at baseline, among subsamples at 12-month intervals, and for all alive at 60 months. Cumulative BP was calculated as the average between baseline and follow-up measures multiplied by the time between them (mmHg × year). Linear mixed models were used to assess the effects of salt substitution on BP outcomes at each follow-up visit. After a mean 4.74 years of follow-up, salt substitute compared to the regular salt lowered the cumulative SBP with a mean (SD) of 740 (85) vs. 750 (87) mmHg×year. Salt substitute also lowered cumulative MAP and PP, with means (SD) of 560 (58) vs. 566 (59) mmHg×year, and 306 (67) vs. 313 (68) mmHg×year, respectively. Similar beneficial effects of the salt substitute were observed for traditional measurements of SBP, MAP, and PP. There was no difference in either cumulative DBP (434 vs. 437 mmHg × year) or traditional DBP (85 vs. 86 mmHg). Salt substitute significantly reduced cumulative and traditional SBP, MAP, and PP, but not DBP. TRIAL REGISTRATION: SSaSS ClinicalTrials.gov number: NCT0 2,092,090.