BACKGROUND: Cerebral cavernous malformations (CCM) are enlarged vascular lesions 
affecting 0.1-0.5% of the population worldwide and causing hemorrhagic strokes, 
seizures, and neurological deficits. Familial CCM type 1 (CCM1) is an autosomal 
dominant disease caused by mutations in the Krev Interaction Trapped 1 
(KRIT1/CCM1) gene, and is characterized by multiple brain lesions whose number 
and size increase with age. The number of lesions varies widely for unknown 
reasons, even among carriers of similar ages with the same mutation. The purpose 
of this study was to investigate whether cardiovascular (CV) risk factors 
influence potential markers of familial CCM1 disease severity, such as lesion 
count and history of intracerebral hemorrhage.
METHODS: We analyzed baseline data from 185 Hispanic subjects, enrolled in the 
Brain Vascular Malformation Consortium study between June 2010 and March 2013. 
All subjects were carriers of the founder Q455X 'Common Hispanic Mutation' (CHM) 
in the KRIT1 gene, and had a clinical diagnosis of CCM or had an affected first- 
or second-degree relative with CCM. We performed a cross-sectional study, 
collecting detailed clinical information of CCM1-CHM subjects and cerebral 
susceptibility-weighted magnetic resonance imaging to assess lesion count. 
Linear or logistic regression analysis of log-lesion count or history of 
intracerebral hemorrhage and CV risk factors (age, gender, obesity, diabetes, 
hypertension, hyperlipidemia and smoking status) and related quantitative traits 
(body mass index, glycosylated hemoglobin levels, blood pressure, lipids levels 
and pack-years of cigarette smoking) was performed accommodating familial 
clustering.
RESULTS: CCM1-CHM subjects were mainly female (63.8%) and symptomatic at 
presentation (63.2%). Lesion count was highly variable (mean ± SD: 57.7 ± 110.6; 
range: 0-713); 90% of CCM1-CHM subjects had multiple lesions at enrollment. Age 
(p < 0.001) was positively correlated with lesion count and male gender (p = 
0.035) was associated with a greater number of lesions. Obesity (p = 0.001) and 
higher body mass index (p = 0.002) were associated with fewer lesions. No 
association with hypertension was detected, however, systolic blood pressure (p 
= 0.002) was associated with fewer lesions. No significant association with 
lesion count was observed for diabetes, hyperlipidemia, smoking status or for 
related quantitative traits. History of intracerebral hemorrhage was not 
significantly associated with any CV risk factors, however, we found borderline 
associations of hemorrhage with obesity (p = 0.062), systolic blood pressure (p 
= 0.083) and pack-years of cigarette smoking (p = 0.055). After correction for 
multiple testing, age and obesity remained significantly associated with lesion 
count in CCM1-CHM subjects.
CONCLUSIONS: These results suggest that several CV risk factors explain some of 
the variability in lesion count in Hispanic CCM1-CHM subjects. Although age, 
gender, obesity, body mass index and systolic blood pressure may influence 
familial CCM1 disease severity, further longitudinal studies in larger sample 
sizes are essential to confirm these findings.