What are the risk factors for cerebral small vessel disease (CSVD)?

From the Guidelines

Small vessel disease is primarily caused by hypertension, diabetes, and aging, with hypertension being the most significant modifiable risk factor, as evidenced by the 2022 guideline for the management of patients with spontaneous intracerebral hemorrhage 1. The risk factors for small vessel disease can be categorized into two main types: arteriolosclerosis and cerebral amyloid angiopathy (CAA).

• Arteriolosclerosis is associated with hypertension, diabetes, and age, and is typically found in deep territories of the brain, such as the basal ganglia, thalamus, brainstem, and deep cerebellar nuclei 1.
• CAA is defined by deposition of β-amyloid peptide in the walls of arterioles and capillaries, and is associated with age and apolipoprotein E genotypes containing the ε2 or ε4 alleles 1. Other important risk factors for small vessel disease include hyperlipidemia, obesity, physical inactivity, excessive alcohol consumption, and poor sleep.
• The management of these risk factors is crucial in preventing small vessel disease, with recommendations including blood pressure targets below 130/80 mmHg, glycemic control aiming for HbA1c <7%, complete smoking cessation, and regular exercise 1.
• Additionally, lifestyle modifications such as a Mediterranean diet, limited alcohol intake, and adequate sleep are also recommended 1. It is essential to note that early intervention against these risk factors is crucial, as small vessel disease can lead to cognitive decline, stroke, and physical disability if left unaddressed.
• The 2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease also emphasizes the importance of risk factor management, including hypertension, hypercholesterolemia, diabetes, and smoking cessation 1.

From the Research

Small Vessel Disease Risk Factors

• The risk factors for small vessel disease (SVD) include hypertension, diabetes, hyperlipidemia, and smoking, as identified in a meta-analysis of 29 studies involving 16,587 participants 2
• Additionally, sedentary existence, obesity, and poor sleep patterns are recognized drivers of SVD, while depression is now recognized as a vascular risk factor 3
• Inflammation is a mediator of SVD, but it is not known which factor(s) predominate in its etiology 3
• Genetic predisposition to higher systolic and diastolic blood pressure, diabetes, obesity, smoking, and higher triglyceride levels are associated with an increased risk of lacunar stroke and cerebral small vessel disease (CSVD) 4
• On the other hand, genetic predisposition to higher HDL concentrations and moderate-to-vigorous physical activity are associated with a lower risk of lacunar stroke and CSVD 4

Modifiable Risk Factors

• Hypertension is the most important modifiable risk factor for stroke, and efficacious reduction of blood pressure is essential for stroke prevention 5
• Treatment of dyslipidemia with statins, anticoagulation therapy in atrial fibrillation, and carotid endarterectomy in symptomatic high-grade carotid stenosis are also effective for stroke prevention 5
• Lifestyle factors that have been proven to reduce stroke risk include reducing salt, eliminating smoking, performing regular physical activity, and maintaining a normal body weight 5

Medical Interventions

• Antihypertensive therapy, including angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and calcium antagonists, can be effective in managing hypertension and reducing the risk of cardiovascular morbidity and mortality 6
• Calcium channel blockers (CCBs) have been associated with a lower risk of lacunar stroke and CSVD, while Cholesteryl Ester Transfer Protein (CETP) inhibitors, lipoprotein lipase (LPL), and gastric inhibitory polypeptide receptor (GIPR) may also have beneficial effects on CSVD 4