Arteries widening rather than becoming blocked could be the trigger for lacunar strokes, the small vessel strokes that affect tens of thousands of people in Britain each year, according to new research that challenges decades of medical orthodoxy.
Scientists at the University of Edinburgh have found that lacunar strokes — which damage tiny blood vessels deep within the brain — may stem from arterial dilation, not constriction or fatty deposits. The finding upends the conventional assumption that blockages are the primary culprit and may explain why standard treatments such as antiplatelet drugs have proved ineffective for this stroke subtype.
Arterial Widening Linked to Fourfold Increase in Risk
The study, published in the journal Circulation, tracked 229 individuals who had suffered either a lacunar or mild non-lacunar stroke. Each participant underwent comprehensive brain imaging and cognitive assessments at the time of their stroke, with follow-up examinations conducted twelve months later. Researchers monitored indicators of small vessel disease alongside any fresh areas of brain damage.
Their analysis revealed a striking pattern: enlargement of arteries, rather than constriction, was associated with lacunar stroke. Patients with widened arteries faced a fourfold increase in their likelihood of experiencing this type of stroke. Conversely, narrowing of large arteries was not significantly linked to lacunar stroke or small vessel disease. The widening was also associated with a greater burden of small vessel disease and a higher risk of developing silent strokes — events that occur without obvious symptoms but are a significant indicator of vascular health. High blood pressure is identified as the most significant cause of silent strokes in the UK.
Lacunar strokes represent roughly one-fifth of all strokes nationally, according to British Heart Foundation estimates, affecting approximately 35,000 people across Britain each year. They can cause lasting difficulties with cognition, memory and movement, and may progress to dementia. Problems with small brain blood vessels are a major contributor to vascular dementia.
Study Reveals Silent Strokes Despite Preventative Treatment
The research also uncovered that more than a quarter of patients suffered silent strokes during the study period, despite receiving preventative treatment. These silent cerebral infarctions increase the risk of major strokes and vascular dementia. Established risk factors for lacunar stroke include high blood pressure, type 2 diabetes and smoking.
Professor Joanna Wardlaw, who leads applied neuroimaging at Edinburgh’s Institute for Neuroscience and Cardiovascular Disease and serves as group leader at the UK Dementia Research Institute, said: “This study provides strong evidence that lacunar stroke is not caused by fatty blockage of larger arteries, but by disease of the small vessels within the brain itself.
“Recognising this distinction is crucial, because it explains why conventional treatments like anti-platelet drugs are not as effective for this type of stroke and highlights the urgent need to develop new therapies that target the underlying microvascular damage.”
Professor Wardlaw, who also holds an Honorary Consultant Neuroradiologist position with NHS Lothian and established the Brain Research Imaging Centre at Edinburgh and the Scottish Imaging Network, has previously influenced global stroke treatment guidelines through her work on cerebral small vessel disease.
Implications for Treatment and Future Research
The findings have direct implications for patient care. Traditional stroke treatments designed to prevent blockages — such as aspirin and other antiplatelet drugs — appear to be less effective for lacunar strokes because the underlying mechanism is different. The research is already informing further clinical work, including the LACunar Intervention Trial 3 (LACI-3), which is examining whether existing medications might prove effective against this particular form of stroke.
LACI-3 is a large-scale Phase 3 clinical trial that aims to recruit 1,300 participants, with a primary outcome focused on cognitive function. The trial is testing two existing drugs — cilostazol and isosorbide mononitrate — to see if they can protect the brain, reduce further strokes, and prevent cognitive decline and mobility problems in patients with lacunar stroke. Previous trials, LACI-1 and LACI-2, showed these drugs to be safe and well-tolerated, with LACI-2 demonstrating promising results in reducing recurrent strokes, dependency and cognitive impairment. This approach is an example of drug repurposing, using medications already licensed for other conditions such as heart and circulatory diseases.
The research was funded by a consortium including the UK Dementia Research Institute (supported by the UK Medical Research Council, Alzheimer’s Society, and Alzheimer’s Research UK), the Leducq Foundation, the Stroke Association, British Heart Foundation, Scottish Government’s Chief Scientist Office, Row Fogo Charitable Trust, and Wellcome Trust.
Maeva May, Director of Policy at the Stroke Association, said: “Stroke research is chronically underfunded, with less than one per cent of total UK research funding spent on the condition. Yet these findings illustrate the value of research and the potential it has to change the lives of stroke patients. This study and more of its kind need to be a national priority across the NHS, government and the wider research community with clear pathways to carry breakthrough discoveries from laboratory to patients.”