Small‐Vessel Disease in the Heart and Brain: Current Knowledge, Unmet Therapeutic Need, and Future Directions

I schemic heart disease (IHD), stroke, and dementia are leading causes of death and disability worldwide, notably affecting aging populations. The public health burden related to chest pain is substantial and the epidemiology of IHD because of large-vessel coronary atherosclerosis is well documented. By contrast, the epidemiology of small-vessel disease (SVD) in the heart is less well established. Cohort studies indicate that the underlying cause of anginal chest pain may be SVD in more than 1 in 3 of all-comers with stable symptoms. IHD because of SVD associates with vascular risk factors, such as hypertension and female sex. The vascular anatomy of the heart and brain is similar in that conduit arteries are distributed on the surface of these organs with tissue perfusion achieved through deep penetrating arteries. In the heart, SVD involves the deep penetrating coronary arterioles and the subendocardial plexus of microvessels. The clinical sequelae of SVD in the heart include stable and acute coronary syndromes and heart failure in the longer term. SVD in the brain mainly involves small subcortical cerebral arteries. Occlusion of 1 of these vessels may result in a clinical stroke syndrome known as a lacunar syndrome. Acute imaging may show a lesion (<20 mm) on diffusion-weighted magnetic resonance imaging (MRI) indicating an acute lacunar infarct. Later imaging may continue to identify the resulting end-stage lesion as a lacune (<15 mm). Long-term ischemia from SVD may show only white matter hyperintensities with or without lacunes and may manifest as vascular cognitive impairment. SVD may manifest as a multisystem disorder implying commonality between disorders of small vessels of the heart and brain (and potentially other organs such as the kidney) (Figure 1). In this article, we review the co-existence of SVD in heart and brain. We consider evidence for and against a pathophysiological link between SVD in the heart and brain. We identify gaps in knowledge and disease-modifying therapy. Clinical cases are presented in Figure 2.