moyamoya disease ( mmd ) is known as a progressive steno - occlusive intracranial angiopathy with small , fragile , and multiple collateral formation ( 1 ) . the prevalence of mmd was found to be 16.1 per 100,000 in the republic of korea , when calculated with the 2011 population ( 2 ) . the mmd is usually known to involve intracranial arteries , but systemic involvement of endothelial hyperplasia was raised in an autopsy study ( 3 ) . also , the renal artery is often involved with this disease in around 8% of the cases ( 4 ) . it has been reported that the systemic arterial involvement in mmd can be a manifestation of certain genetic mutation such as acta 2 ( 5 ) . up to date , coronary artery disease in mmd has been described sporadically in several case reports , and the association between mmd and coronary heart disease ( chd ) has been constantly suggested in the literature ( 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ) . however , to the best of our knowledge , there have been no reports determining the prevalence of symptomatic chd in mmd . in this study , we retrospectively reviewed the adult patients in mmd registry to determine the prevalence of chd . also , we explored the potential risk factors and analyzed the characteristics of chd in mmd . from january 1995 to december 2012 , 456 consecutive adult patients (  20 yr of age ) with mmd visited our hospital and were registered as adult mmd patients . the diagnosis of mmd was made based on idiopathic steno - occlusion at the terminal portion of internal carotid artery with concomitant abnormal vascular networks in the vicinity of the steno - occlusive lesions , which was confirmed by conventional angiography and/or magnetic resonance imaging . all clinical data including coronary evaluation and medical history from our adult mmd registry were reviewed by two neurosurgeons . to obtain possible missing data from manual analyses , data collection of chd was also performed using computerized queries , retrieving all coronary angiographic details and discharge summaries in the registry . the chd patients were identified by searching with the keywords " coronary artery " , " angina " , or " myocardiac infarction " . chd was defined as typical chest pain with corresponding coronary artery lesion on imaging study . the following explanatory variables were assessed : age , gender , type of mmd , and clinical risk factors that were known for causes of atherosclerosis and chd , such as hypertension , diabetes mellitus ( dm ) , smoking and dyslipidemia ( 15 ) . the different types of mmd were categorized according to clinical symptoms at the initial diagnosis with mmd as follows : ischemic , hemorrhagic , asymptomatic , and atypical symptoms , such as headache and dizziness . to explore the potential risk factors of chd in mmd , statistical analyses were performed . mann - whitney u - test was performed , and multiple logistic regression test was performed for multivariate analysis . statistical analysis was performed using spss 20.0 software ( spss , chicago , il , usa ) . this study was approved by the institutional review board of the samsung medical center ( irb no . from january 1995 to december 2012 , 456 consecutive adult patients (  20 yr of age ) with mmd visited our hospital and were registered as adult mmd patients . the diagnosis of mmd was made based on idiopathic steno - occlusion at the terminal portion of internal carotid artery with concomitant abnormal vascular networks in the vicinity of the steno - occlusive lesions , which was confirmed by conventional angiography and/or magnetic resonance imaging . all clinical data including coronary evaluation and medical history from our adult mmd registry were reviewed by two neurosurgeons . to obtain possible missing data from manual analyses , data collection of chd was also performed using computerized queries , retrieving all coronary angiographic details and discharge summaries in the registry . the chd patients were identified by searching with the keywords " coronary artery " , " angina " , or " myocardiac infarction " . chd was defined as typical chest pain with corresponding coronary artery lesion on imaging study . the following explanatory variables were assessed : age , gender , type of mmd , and clinical risk factors that were known for causes of atherosclerosis and chd , such as hypertension , diabetes mellitus ( dm ) , smoking and dyslipidemia ( 15 ) . the different types of mmd were categorized according to clinical symptoms at the initial diagnosis with mmd as follows : ischemic , hemorrhagic , asymptomatic , and atypical symptoms , such as headache and dizziness . to explore the potential risk factors of chd in mmd , statistical analyses were performed . mann - whitney u - test was performed , and multiple logistic regression test was performed for multivariate analysis . statistical analysis was performed using spss 20.0 software ( spss , chicago , il , usa ) . this study was approved by the institutional review board of the samsung medical center ( irb no . the median follow - up period was 32 months ( range , 1 - 192 ) . during the follow - up period the sudden death could have been caused by coronary heart disease , but there was no definite evidence associated with it as a cause of death , because medical examination could not be performed . the median age at chd diagnosis was 44 yr ( range , 27 - 59 ) . three ( patient no . 7 , 13 , and 14 ) of them were unilateral disease and 4 ( patient no . the treatment for chd were as follows : 11 medical treatments ( 5 variant angina with mild degree of stenosis , 6 stable angina ) , 4 coronary artery bypass graft ( cabg ) , and 6 percutaneous coronary intervention ( pci ) . the patients with chd were older in age ( median , 46 ; range , 20 - 63 ) when diagnosed with mmd than the patients who were diagnosed as mmd without chd ( median age , 39 ; range , 20 - 76 ; p=0.003 , mann - whitney u - test ) . the patients with mmd and chd had higher percentage of dm than the mmd patients without the chd ( 23.8% vs. 8.2% , p=0.031 fisher 's exact test ) . multivariate analyses using multiple logistic regression test showed that only the age factor was associated in those with both chd and mmd ( p=0.021 , or , 1.053 ; 95% ci , 1.008 - 1.110 ) . other variables , such as gender , hyperlipidemia , hypertension , smoking , and subtype of mmd ( hemorrhagic vs. ischemic vs. atypical vs. asymptomatic ) were not statistically different between those with and without chd ( table 3 ) . coronary computed tomography angiography ( cta ) was available for 7 patients , and 4 patients showed no calcification of affected coronary artery ( fig . several of the previous reported articles demonstrated chd in mmd , and most of them were reported from east asian countries ( 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 16 ) . ikeda demonstrated that mmd is involved with the extra - cranial vessels as well as the intracranial vessels , and there are systemic etiologic factors , which cause intimal thickening in the systemic vessels ( 3 ) . histopathologic studies of the involved internal carotid arteries in mmd showed fibrocellular thickening of the intima and proliferated smooth muscle cells ( smc ) as the cause of the arterial occlusion ( 17 , 18 ) . also , the smc proliferation is part of the mechanism of atherosclerosis in chd , which is similar to the histopathology of mmd ( 19 , 20 ) . several mutant genes which can cause stenosis in both mmd and chd have already been reported ( 5 , 17 ) . if these two diseases had significant association , screening test should be performed to reduce the morbidity and mortality . in our adult mmd registry , however , this percentage could be underestimated because only the symptomatic patients who underwent diagnostic study at our hospital were retrospectively included . the prevalence of chd in the asian population is known to be less than 1% person per year in the population of 65 or less years of age ( 21 ) , which could be significant . in this study , all of the chd were developed at relatively young age ( < 65 yr ) , and framingham scores were low at the initial diagnosis of mmd . also , half of the patients showed no calcification on cta , which reflects the atherosclerotic burden of the coronary artery . these findings support the idea that mmd is a causative factor of chd rather than pure atherosclerosis ( 16 , 22 ) . previous case reports about chd in mmd described the minimal atherosclerotic burden on the affected coronary artery ( 10 , 16 ) , and half of our data supported this except the coronary artery lesions were heterogeneous in this study . the prevalence was not high enough to designate mmd as the main culprit . also , in this study the classic risk factors for atherosclerosis , such as old age and diabetes , were associated with chd in mmd . therefore , we hypothesized that the underlying endothelial hyperplasia in the coronary artery is not so significant in the most cases of mmd , but smaller atherosclerotic burden seemed to be causing the symptomatic chd in mmd patients at younger age than normal population . in our study , 5 ( 23.8% ) of 21 chd patients were diagnosed as variant angina , and this proportion was high compared with general chd patients . in 1998 , ikeda et al . , reported variant angina associated with mmd , and 2 ( 22.2% ) out of 9 mmd patient were diagnosed as variant angina ( 23 ) however , there has been no evidence that supports this idea , considering the mechanism of variant angina and mmd . also , not all of the patients underwent coronary cta , which could have provided more information about atherosclerotic components , such as calcium score or plaque content . the mmd is a rare disease and there is no adequate evidence regarding the association between chd and mmd , which makes it difficult to perform a prospective , controlled study . this study also reflects mainly the patients who were treated in our hospital . since we have considered those with chd treated in other hospitals , there are some loss of data from outside medical records . therefore , the prevalence suggested in this study might be underestimated . in conclusion , mmd does not seem to be the main culprit of chd , but it can lead to chd with small atherosclerosis probably due to the underlying endothelial proliferation . the screening test for chd in the mmd patients with older age is in need , and dm might have a role for this matter . the future study with a larger sample size is warranted to reveal the general characteristics of chd in mmd and to determine the usefulness of coronary screening test in mmd .
the purpose of this study was to determine the prevalence and characteristics of symptomatic coronary heart disease ( chd ) in patients with moyamoya disease ( mmd ) . 
 this retrospective study evaluated 456 patients who received examination for mmd between 1995 and 2012 . 
 we reviewed the patients ' medical history and coronary imaging , including conventional coronary angiography and coronary computed tomography angiogram ( cta ) . among 456 patients with mmd , 21 ( 4.6% ) patients 
 were found to have symptomatic chd . 
 ten patients were treated with coronary artery bypass graft or percutaneous coronary intervention for unstable angina or myocardial infarction . 
 eleven were treated with medication for stable angina ( n = 6 ) and variant angina with mild degree of stenosis ( n = 5).the median age of these patients was 44 yr ( range , 27 - 59 ) . the median framingham score at diagnosing mmd was < 1% ( range , < 1%-16% ) . 
 the old age was associated with chd in uni- and multivariate analyses ( p = 0.021 , or , 1.053 ; 95% ci , 1.008 - 1.110 ) . 
 considering low age of onset and low stroke risk factor , chd might be a systemic manifestation that is clinically relevant to mmd.graphical abstract