This study included a total of 1397 patients with CAA during 2005–2011. The mean age of our population was 37.76 ± 31.45 years. Notably, the age distribution ranged widely from 0 to 91 years in our study, and the pediatric, adult and elderly populations accounted for 41.9, 30.8 and 27.3% of the total, respectively. In contrast with angiographic series in the literature, we had access to the data of pediatric patients with CAA instead of only adults. The mean age of the pediatric population was 3.16 ± 3.66 years, and approximately 69.3% of the pediatric patients were male.
Comorbidities in pediatric patients
Most pediatric patients were diagnosed with Kawasaki disease (95.7%), especially infants 1 year of age and below (23.2%), and were under 5 years of age, which was in accordance with epidemiological reports in Taiwan [23,24,25].
Kawasaki disease is a systemic vasculitis that commonly involves the coronary arteries and is considered the main cause of nonatherosclerotic CAA in young children [20, 22]. From our results, the disease burden of Kawasaki disease in Taiwan and its associated risk for the development of CAA cannot be overlooked. For young patients presenting acute coronary syndrome, such as angina and myocardial infarction, the development of CAA should be considered and patients should receive treatment as soon as possible.
Comorbidities in adult patients
The mean age of the adult population with CAA was 62.9 ± 14.1 years, and the majority of patients were male (67.9%). Prevalent coexisting diseases included hypertension (63.4%), hyperlipidemia (39.6%), diabetes mellitus (26.1%) and other chronic diseases. A small proportion of CAA patients had aortic dissection and aortic aneurysm. Most of the comorbidities were diagnosed more frequently after identification of CAA. Remarkably, coronary atherosclerosis was found in 72.5% of patients after CAA diagnosis.
Atherosclerosis remains the principal cause of CAA in the adult population, even though the exact etiology is still unknown [22, 26]. Our results showed a high proportion of coronary atherosclerosis (72.5%) in adults, which was consistent with the literature. With respect to cardiovascular diseases, our patients had a higher incidence of hypertension and diabetes mellitus but a lower incidence of hyperlipidemia than those in other reports in general. The variation may be due to the relatively older age of our population. Hypertension, hyperlipidemia and diabetes mellitus are risk factors known to be associated with atherosclerosis; however, the relationship between risk factors of hypertension, hyperlipidemia, diabetes mellitus and CAA needs to be further investigated.
Previous myocardial infarction and angina were reported in 10.4 and 18.9% of our population, respectively; these proportions were lower than those in some previous studies [21, 27, 28]. It has been suggested that patients with CAA commonly present with ischemic heart disease such as angina pectoris and myocardial infarction. Nevertheless, it was difficult to differentiate whether these symptoms were manifestations of aneurysm or coronary artery disease .
Prescribing patterns in pediatric patients
In the current study, we found an increased utilization of aspirin and gamma globulins in 82.9 and 53.6% of pediatric patients, respectively, after CAA diagnosis. Among the antithrombotic agents, aspirin was used most frequently, followed by dipyridamole (16.9%), heparin (5.8%) and warfarin (4.6). Only 4 patients (0.7%) received clopidogrel. Since most of the pediatric patients (95.7%) were diagnosed with Kawasaki disease, antithrombotic treatments were reasonably used in the clinic. On the basis of the recommendations by the American Heart Association (AHA) guidelines , aspirin should be administered at a high dosage (80 to 100 mg/kg/day) with intravenous immunoglobulin (IVIG) in the acute phase because these two medications appear to possess an additive anti-inflammatory effect. However, the duration of high-dose aspirin treatment differs by institution, and most reduce the aspirin dose 48 to 72 h after fever subsides. In certain cases, the duration may be prolonged to 14 days after Kawasaki disease onset.
Aspirin treatment should be adjusted to a low dosage (3 to 5 mg/kg/day) after the acute phase. Platelet aggregation activity remains high during the first 3 months after Kawasaki disease onset and can even last for 1 year after disease onset in some cases. For patients who develop coronary aneurysm due to Kawasaki disease, aspirin may be continued indefinitely to prevent ischemic heart disease and prevent the formation or growth of thrombi by platelet aggregation based on the Japanese Circulation Society (JCS) guidelines . Suggested antiplatelet agents to be used in children with Kawasaki disease include aspirin, flurbiprofen, dipyridamole, ticlopidine and clopidogrel. Choices for anticoagulant drugs include heparin, low-molecular weight heparin (LMWH) and warfarin. In view of the existing CAAs in our patients with Kawasaki disease, antiplatelet treatment for the prevention of cardiac sequela is reasonable.
Prescribing patterns in adult patients
Regarding medication use in adult patients, we found that antithrombotic agents, particularly aspirin, clopidogrel and heparin, were prescribed more frequently after CAA diagnosis. Cardiovascular medications, oral antidiabetic agents, lipid-lowering agents and nitrates, were also increasingly prescribed after CAA diagnosis. Among the prescriptions, aspirin (75.8%), β-blockers (48.3%), statins (47.6%), metformin (14.4%), sulfonylureas (14.4%) and isosorbide mononitrate (32.9%) were frequently observed in each category. Data regarding prescribing patterns in CAA patients was limited in the previous literature. Most series focused on whether patients received surgery, percutaneous intervention or medical therapy instead of specific drug utilization. Only a few studies reported the prescribing pattern in patients with CAA [31, 32]. Sultana et al.  reported that 56, 14 and 70% of patients were prescribed aspirin, warfarin and a combination of aspirin and warfarin, respectively. Other medications, such as calcium channel blockers (CCBs), β-blockers and nitrates, were used in 25, 20 and 34% of patients, respectively. A 97% prescribing rate for aspirin was reported in a series by Almansori et al.,  in which angiotensin-converting-enzyme (ACE) inhibitors (59%), angiotensin II receptor blockers (ARBs) (34%), CCBs (22%), statins (95%) and nitrates (49%) were also recorded. The great variety of prescribing patterns across studies was mainly affected by coexisting diseases. A previous review by Dahhan  suggested that the management of coronary artery ectasia should be based on the underlying etiology. The general medical therapy for patients with coronary artery ectasia includes antiplatelet agents, β-blockers, ACE inhibitor, ARBs, CCBs and statins, especially if another indication is present (e.g., hypertension, dyslipidemia, diabetes mellitus).
Concerning the effect of specific medications, antiplatelets, β-blockers and statins are indicated for accompanying atherosclerotic coronary artery disease. In addition, other drugs have different indications: anticoagulants for secondary prevention of further thrombosis; dihydropyridine CCB for the prevention of vasospasm; and ACE inhibitors for decreasing inflammation.
Our study showed that patients under 20 years of age are exposed to acute respiratory infections, noninfectious gastroenteritis and colitis, allergic rhinitis and contact dermatitis very often. There may be a relationship between Kawasaki disease with allergic diseases and this finding is consistent with previous studies [34, 35]. Kawasaki disease were at an increased risk for allergic diseases compared with the comparison cohort and children with Kawasaki disease had a higher risk of developing atopic dermatitis.
In summary, the management of CAA should be tailored to each individual based on the underlying etiology. Our adult population had a significant burden of cardiovascular disease, which indicated that drugs prescribed for such chronic conditions were reasonable.
To the best of our knowledge, this is the first population-based study investigating the comorbidities and prescribing patterns for CAA patients in Taiwan. We enrolled CAA population in Taiwan, with data obtained from the NHIRD. We are able to provide an explicit age distribution, including pediatric and adult populations, which was different from previous studies that used an angiographic method to enroll adult patients. However, there were some limitations in our study. First, our data were obtained from a claim-based database, and we did not have information on aneurysm features, including the location, morphology, aneurysm size, number of aneurysms and degree of stenosis. In addition, we could not differentiate between CAAs and coronary artery ectasia in this study. Second, we did not have laboratory or image data to determine the severity of artery stenosis, blood pressure values and hemoglobin A1c levels. Some cardiovascular risk factors, such as smoking and body mass index, were also unavailable in the database.