Letter by Cuglan et al Regarding Article, "Characteristics of Intracranial Aneurysms According to Levels of Coronary Artery Calcium".

To the Editor: We have read with great enthusiasm the article recently published by Cho et al. In their retrospective, cross-sectional study they investigated the relationship between the presence of intracranial aneurysms (IAs) and the level of coronary artery calcium (CAC) in 4934 subjects. Briefly, they have found that the prevalence of IA increased with CAC score; 172 (4.8%) subjects with a zero CAC score had IAs, 49 (5.4%) with a low CAC score, 22 (6.4%) with an intermediate CAC score, and 15 (11.1%) with a high CAC score (P for trend, 0.004). Additionally multivariate logistic regression has shown that high CAC score is an independent risk factor for the presence of IA compared with zero CAC score (adjusted odds ratio, 2.16; 95% CI, 1.18–3.95). And they have underlined the role of atherosclerosis in development of IAs. Although the pathophysiology of IA shares common risk factors of atherosclerosis, such as hypertension, dyslipidemia, the exact mechanism remains unknown. Major risk factors of atherosclerosis, such as hypertension, smoking, hyperlipidemia, and diabetes mellitus, are insufficient to explain the pathogenesis of IAs. Likewise, Cho et al has reported that only hypertension among the cardiovascular risk factors is associated with IA. It is of note that diabetes mellitus has been reported to have a protective role against vascular dilatation such as coronary artery ectasia (CAE), abdominal aortic aneurysm an even subarachnoid hemorrhage of IA. The pathogenesis of IA involves persistent pathological vascular remodeling with proteolysis/extracellular matrix degradation via matrix metalloproteinases, cathepsin enzymes, oxidative stress, and apoptosis with concomitant vessel wall inflammation eventually resulting in aneurysm formation. Additionally multiple aneurysms have been found in 15% to 45% of patients with IA, suggesting that a substantial number of patients are naturally aneurysm prone. Moreover, association of IA with abdominal aortic aneurysm has been reported in literature reviewed by Yetkin et al. CAC, known to be a marker of overall atherosclerotic plaque burden, has been shown to be a predictor of future cardiovascular risk independent of conventional risk scores. However, coronary calcification has also been reported in another form of dilating vascular disease, CAE in which functional loss of musculoelastic components of vascular wall media is considered to be predominant aspect of pathophysiology and local manifestation of systemic vascular wall abnormality. CAC score was associated with increased abdominal aorta diameter but not with thoracic aorta diameter. CAC score and prevalence of ascending aorta aneurysm have been shown to be significantly higher in CAE patients compared with patients having no ectasia. Increased coronary calcium score has been reported in patients with coronary artery aneurysm due to Kawasaki Disease which is a nonatherosclerotic inflammatory disease. It might be helpful to improve our understanding on the pathophysiology of both IA and CAE if the authors could give the distribution of coronary artery disease and the presence of CAE in addition to CAC score. We agree with the authors that different pathophysiological mechanisms other than seen in atherosclerosis might play a role in the formation of IA. Atherosclerosis per se is not sufficient to explain the mechanism of IA and other dilating vascular disease. In this regard, the CAC score might indicate not only the atherosclerotic burden and cardiovascular event risk but also the tendency to dilate or aneurysm formation in prone subjects.