Risk factors for small vessel disease in adults with atherosclerosis: a systematic review and meta-analysis

Atherosclerosis is marked by irregular intimal plaques, known as atheroma, which intrude into the lumen of medium-sized and large arteries. Small vessel disease (SVD) is a major contributor to stroke and cognitive impairment and frequently coexists with atherosclerosis due to shared vascular risk factors and overlapping pathophysiological mechanisms. This meta-analysis aimed to systematically evaluate the association between atherosclerotic risk factors and the development of SVD in adult and elderly populations. A systematic review and meta-analysis were conducted in accordance with PRISMA 2020 guidelines. PubMed, ScienceDirect, Elsevier, and Google Scholar were searched for eligible studies published between January 2000 and October 2023. Community-based randomized controlled trials and observational studies assessing atherosclerotic risk factors and SVD-related outcomes, primarily carotid intima-media thickness and carotid plaque, were included. Data were pooled using a random-effects model. Heterogeneity was assessed using the I² statistic, and publication bias was evaluated using funnel plots and sensitivity analyses. Across 11 studies with sample sizes ranging from 50 to 5,585 participants, age and hypertension consistently demonstrated the strongest associations with SVD. Age showed an odds ratio of 1.07 (95% CI: 1.03–1.11; p = 0.0001), while hypertension yielded a pooled odds ratio of 2.24 (95% CI: 1.90–2.64; p < 0.0001). Diabetes was also significant (OR 1.38; p < 0.0001), whereas metabolic syndrome was not (p = 0.69). The study concludes that hypertension, age, diabetes mellitus, and carotid atherosclerotic markers—particularly carotid plaque—are significant predictors of SVD.