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Vol. 180, No. 6 DOI: 10.1093/aje/kwu169 Advance Access publication: August 13, 2014
Original Contribution Cross-Sectional Comparison of Coronary Artery Calcium Scores Between Caucasian Men in the United States and Japanese Men in Japan The Multi-Ethnic Study of Atherosclerosis and the Shiga Epidemiological Study of Subclinical Atherosclerosis
* Correspondence to Dr. Akira Fujiyoshi, Department of Public Health, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192, Japan (e-mail: [email protected]).
Initially submitted February 6, 2014; accepted for publication June 3, 2014.
The incidence of coronary heart disease in the United States has declined, and prevalences of several coronary disease risk factors have become comparable to those in Japan. Therefore, the burden of coronary atherosclerosis may be closer among younger persons in the 2 countries. We aimed to compare prevalences of coronary atherosclerosis, measured with coronary artery calcium scores, between men in the 2 countries by age group (45–54, 55–64, or 65–74 years). We used community-based samples of Caucasian men in the United States (2000– 2002; n = 1,067) and Japanese men in Japan (2006–2008; n = 832) aged 45–74 years, stratifying them into groups with 0, 1, 2, or ≥3 of the following risk factors: current smoking, overweight, diabetes, dyslipidemia, and hypertension. We calculated adjusted odds ratios of US Caucasian men’s having Agatston scores of ≥10, ≥100, and ≥400 with reference to Japanese men. Overall, the odds of Caucasian men having each Agatston cutoff point were greater. The ethnic difference, however, became smaller in younger age groups. For example, adjusted odds ratios for Caucasian men’s having an Agatston score of ≥100 were 2.05, 2.43, and 3.86 among those aged 45–54, 55–64, and 65–74 years, respectively. Caucasian men in the United States had a higher burden of coronary atherosclerosis than Japanese men, but the ethnic difference was smaller in younger age groups. atherosclerosis; coronary artery calcium; ethnic group; men
Abbreviations: BMI, body mass index; CAC, coronary artery calcium; CDC, Centers for Disease Control and Prevention; CHD, coronary heart disease; CT, computed tomography; CRMLN, Cholesterol Reference Method Laboratory Network; EDTA, ethylenediaminetetraacetic acid; HU, Hounsfield Units; ICC, intraclass correlation coefficient; MESA, Multi-Ethnic Study of Atherosclerosis; SESSA, Shiga Epidemiological Study of Subclinical Atherosclerosis.
levels in Japan and the United States, particularly among middle-aged men (2). For example, serum total cholesterol levels have steadily increased in Japanese men aged 40–49 years since the 1960s, while those in US men have decreased, reaching levels (200–210 mg/dL) that are comparable between the 2 countries (2). Moreover, epidemiologic studies conducted in different areas of Japan have indicated a trend
The Seven Countries Study and other evidence previously suggested that Japan had one of the lowest rates of coronary heart disease (CHD) mortality in the developed world, and this was largely attributed to its low serum total cholesterol level in comparison with other countries, including the United States (1, 2). More recently, however, prevalences of several coronary disease risk factors have reached similar 590
Am J Epidemiol. 2014;180(6):590–598
Downloaded from http://aje.oxfordjournals.org/ at Library - Faculty of Medicine Ramathibodi Hospital on March 7, 2015
Akira Fujiyoshi*, Katsuyuki Miura, Takayoshi Ohkubo, Takashi Kadowaki, Sayaka Kadowaki, Maryam Zaid, Takashi Hisamatsu, Akira Sekikawa, Matthew J. Budoff, Kiang Liu, and Hirotsugu Ueshima for the SESSA and MESA Research Groups
CAC Scores Among US and Japanese Men 591
METHODS Study populations
The study population consisted of male participants from 2 cohort studies: MESA in the United States and SESSA in Japan. MESA was designed to study the prevalence, risk factors, and progression of subclinical cardiovascular disease in a multiethnic cohort in the United States. A detailed description of the study design and methods has been published previously (13). In brief, 6,814 participants aged 45–84 years who identified themselves as white, black, Hispanic, or Chinese were recruited from 6 US communities (Forsyth County, North Carolina; northern Manhattan and the Bronx in New York City; Baltimore City and Baltimore County, Maryland; St. Paul, Minnesota; Chicago, Illinois; and Los Angeles County, California) between 2000 and 2002. All participants were free of clinical cardiovascular disease. Only Caucasian men from MESA were analyzed in the present study. SESSA is a study of subclinical atherosclerosis and its determinants in a community-based sample of Japanese residents Am J Epidemiol. 2014;180(6):590–598
(14). Japanese men aged 40–79 years who lived in Kusatsu City, Shiga, Japan, were examined between May 2006 and March 2008. Candidates were identified on the basis of a random sample from the Kusatsu City Basic Residents’ Register, which includes the name, age, and sex of all city residents. All of the participants were without clinical cardiovascular disease or other severe diseases (15). For the present study, we limited our analyses to persons aged 45–74 years at baseline to ensure comparability, as this age range is found in both cohorts. CAC measurements
A detailed description of the method of CAC measurement in MESA has been given elsewhere (16). The protocol used to assess CAC in SESSA was the same as that in the preceding community-based multicenter study (12). In brief, for the 2 protocols, imaging software automatically identified a lesion of candidate CAC on the basis of predefined criteria. Then a reader reviewed each candidate lesion to either accept or reject it and scored the accepted lesions according to the method of Agatston et al. (9). The criteria for automated identification were somewhat different between the 2 protocols. In MESA, 3 criteria needed to be met: computed tomography (CT) attenuation of ≥130 Hounsfield Units (HU), 4 contiguous pixels (1.86 mm2 for 4-detector-row CT; 1.83 mm2 for electron-beam CT), and location within an 8-mm radius of the coronary artery trajectory (16), whereas in SESSA, a CAC lesion was considered to be present with 3 contiguous pixels (1 mm2) with attenuation of ≥130 HU. In MESA, all of the participants were scanned twice, and the average of each Agatston score obtained from the 2 images was used in the analysis (17). In SESSA, participants were scanned once by either electron-beam CT or 16-detector-row CT (18). Based on a study of the duplicate images from 99 SESSA participants read at both imaging centers (i.e., MESA and SESSA), we observed high intraclass correlation coefficients (ICCs) for correlation between MESA and SESSA, regardless of the type of CT (for electron-beam CT, ICC = 0.96 (95% confidence interval: 0.93, 0.98); for multidetector-row CT, ICC = 0.95 (95% confidence interval: 0.91, 0.97)), and we found overall agreement across the levels of Agatston score from 0 to 3,500, with no evidence of systematic difference (18). Other measurements
In MESA, blood pressure was measured 3 times after the participant had rested in a seated position for 5 minutes using a Dinamap Pro 1000 automated oscillometric sphygmomanometer (Critikon Company, Tampa, Florida) and an appropriatesized cuff. The average of the last 2 measurements was used in the analysis. In SESSA, blood pressure was measured twice consecutively on the right arm of the seated participant after the participant had emptied his bladder for urinalysis and had sat quietly for 5 minutes, using an automated oscillometric sphygmomanometer (BP-8800; Omron Colin, Tokyo, Japan) with an appropriate-sized cuff, and the average of the 2 measurements was used. In MESA, a central laboratory (University of Vermont, Burlington, Vermont) measured levels of total and high-density
Downloaded from http://aje.oxfordjournals.org/ at Library - Faculty of Medicine Ramathibodi Hospital on March 7, 2015
of increasing CHD incidence (3, 4), while the overall incidence of CHD in the United States is estimated to have declined in recent years (5–7). Given these changing trends between the United States and Japan, it is of interest to compare the CHD burden between the 2 countries by age group, because there may be graded relationships in CHD burden between the countries across age groups. To obtain a definite answer, one should wait to observe clinical CHD trends in the 2 populations over time, which is time-consuming and labor-intensive. In contrast, comparing subclinical measures of atherosclerosis affords investigators a unique opportunity to obtain insight into the burdens of coronary atherosclerosis. Coronary artery calcium (CAC) level is a well-documented marker for coronary atherosclerosis (8), and the Agatston score (9), a quantitative measure of CAC level, is shown to correlate well with autopsy-confirmed coronary artery plaque levels (10, 11). Therefore, comparison of CAC scores is likely to provide a better assessment of the overall burden of subclinical CHD than a focus on individual risk factors. We have previously shown that middle-aged Japanese men in Japan have a lower burden of CAC than Caucasian men in the United States, even after accounting for traditional risk factors (12). However, the age range of the samples was too narrow (40–49 years) to evaluate the difference by age group. In the present study, we compared community-based samples of men in a broader age range who were recruited from 6 study sites in the United States (the Multi-Ethnic Study of Atherosclerosis (MESA)) and 1 site in Japan (the Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA)). The objectives of the study were: 1) to compare CAC scores between Caucasian men in the United States and Japanese men in Japan, accounting for the different distributions of conventional coronary disease risk factors, and 2) to examine whether the magnitude of the difference in CAC between the 2 populations, if it exists, differed according to age group.
592 Fujiyoshi et al.
Statistical analysis
First, we conducted the following analyses separately according to 10-year age group (45–54, 55–64, and 65–74 years). Each group of participants was further divided into 4 categories according to the presence of the 5 conventional risk factors (number of risk factors = 0, 1, 2, or ≥3). We then calculated the crude prevalences of CAC scores less than 10, 10–
Vol. 180, No. 6 DOI: 10.1093/aje/kwu169 Advance Access publication: August 13, 2014
Original Contribution Cross-Sectional Comparison of Coronary Artery Calcium Scores Between Caucasian Men in the United States and Japanese Men in Japan The Multi-Ethnic Study of Atherosclerosis and the Shiga Epidemiological Study of Subclinical Atherosclerosis
* Correspondence to Dr. Akira Fujiyoshi, Department of Public Health, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192, Japan (e-mail: [email protected]).
Initially submitted February 6, 2014; accepted for publication June 3, 2014.
The incidence of coronary heart disease in the United States has declined, and prevalences of several coronary disease risk factors have become comparable to those in Japan. Therefore, the burden of coronary atherosclerosis may be closer among younger persons in the 2 countries. We aimed to compare prevalences of coronary atherosclerosis, measured with coronary artery calcium scores, between men in the 2 countries by age group (45–54, 55–64, or 65–74 years). We used community-based samples of Caucasian men in the United States (2000– 2002; n = 1,067) and Japanese men in Japan (2006–2008; n = 832) aged 45–74 years, stratifying them into groups with 0, 1, 2, or ≥3 of the following risk factors: current smoking, overweight, diabetes, dyslipidemia, and hypertension. We calculated adjusted odds ratios of US Caucasian men’s having Agatston scores of ≥10, ≥100, and ≥400 with reference to Japanese men. Overall, the odds of Caucasian men having each Agatston cutoff point were greater. The ethnic difference, however, became smaller in younger age groups. For example, adjusted odds ratios for Caucasian men’s having an Agatston score of ≥100 were 2.05, 2.43, and 3.86 among those aged 45–54, 55–64, and 65–74 years, respectively. Caucasian men in the United States had a higher burden of coronary atherosclerosis than Japanese men, but the ethnic difference was smaller in younger age groups. atherosclerosis; coronary artery calcium; ethnic group; men
Abbreviations: BMI, body mass index; CAC, coronary artery calcium; CDC, Centers for Disease Control and Prevention; CHD, coronary heart disease; CT, computed tomography; CRMLN, Cholesterol Reference Method Laboratory Network; EDTA, ethylenediaminetetraacetic acid; HU, Hounsfield Units; ICC, intraclass correlation coefficient; MESA, Multi-Ethnic Study of Atherosclerosis; SESSA, Shiga Epidemiological Study of Subclinical Atherosclerosis.
levels in Japan and the United States, particularly among middle-aged men (2). For example, serum total cholesterol levels have steadily increased in Japanese men aged 40–49 years since the 1960s, while those in US men have decreased, reaching levels (200–210 mg/dL) that are comparable between the 2 countries (2). Moreover, epidemiologic studies conducted in different areas of Japan have indicated a trend
The Seven Countries Study and other evidence previously suggested that Japan had one of the lowest rates of coronary heart disease (CHD) mortality in the developed world, and this was largely attributed to its low serum total cholesterol level in comparison with other countries, including the United States (1, 2). More recently, however, prevalences of several coronary disease risk factors have reached similar 590
Am J Epidemiol. 2014;180(6):590–598
Downloaded from http://aje.oxfordjournals.org/ at Library - Faculty of Medicine Ramathibodi Hospital on March 7, 2015
Akira Fujiyoshi*, Katsuyuki Miura, Takayoshi Ohkubo, Takashi Kadowaki, Sayaka Kadowaki, Maryam Zaid, Takashi Hisamatsu, Akira Sekikawa, Matthew J. Budoff, Kiang Liu, and Hirotsugu Ueshima for the SESSA and MESA Research Groups
CAC Scores Among US and Japanese Men 591
METHODS Study populations
The study population consisted of male participants from 2 cohort studies: MESA in the United States and SESSA in Japan. MESA was designed to study the prevalence, risk factors, and progression of subclinical cardiovascular disease in a multiethnic cohort in the United States. A detailed description of the study design and methods has been published previously (13). In brief, 6,814 participants aged 45–84 years who identified themselves as white, black, Hispanic, or Chinese were recruited from 6 US communities (Forsyth County, North Carolina; northern Manhattan and the Bronx in New York City; Baltimore City and Baltimore County, Maryland; St. Paul, Minnesota; Chicago, Illinois; and Los Angeles County, California) between 2000 and 2002. All participants were free of clinical cardiovascular disease. Only Caucasian men from MESA were analyzed in the present study. SESSA is a study of subclinical atherosclerosis and its determinants in a community-based sample of Japanese residents Am J Epidemiol. 2014;180(6):590–598
(14). Japanese men aged 40–79 years who lived in Kusatsu City, Shiga, Japan, were examined between May 2006 and March 2008. Candidates were identified on the basis of a random sample from the Kusatsu City Basic Residents’ Register, which includes the name, age, and sex of all city residents. All of the participants were without clinical cardiovascular disease or other severe diseases (15). For the present study, we limited our analyses to persons aged 45–74 years at baseline to ensure comparability, as this age range is found in both cohorts. CAC measurements
A detailed description of the method of CAC measurement in MESA has been given elsewhere (16). The protocol used to assess CAC in SESSA was the same as that in the preceding community-based multicenter study (12). In brief, for the 2 protocols, imaging software automatically identified a lesion of candidate CAC on the basis of predefined criteria. Then a reader reviewed each candidate lesion to either accept or reject it and scored the accepted lesions according to the method of Agatston et al. (9). The criteria for automated identification were somewhat different between the 2 protocols. In MESA, 3 criteria needed to be met: computed tomography (CT) attenuation of ≥130 Hounsfield Units (HU), 4 contiguous pixels (1.86 mm2 for 4-detector-row CT; 1.83 mm2 for electron-beam CT), and location within an 8-mm radius of the coronary artery trajectory (16), whereas in SESSA, a CAC lesion was considered to be present with 3 contiguous pixels (1 mm2) with attenuation of ≥130 HU. In MESA, all of the participants were scanned twice, and the average of each Agatston score obtained from the 2 images was used in the analysis (17). In SESSA, participants were scanned once by either electron-beam CT or 16-detector-row CT (18). Based on a study of the duplicate images from 99 SESSA participants read at both imaging centers (i.e., MESA and SESSA), we observed high intraclass correlation coefficients (ICCs) for correlation between MESA and SESSA, regardless of the type of CT (for electron-beam CT, ICC = 0.96 (95% confidence interval: 0.93, 0.98); for multidetector-row CT, ICC = 0.95 (95% confidence interval: 0.91, 0.97)), and we found overall agreement across the levels of Agatston score from 0 to 3,500, with no evidence of systematic difference (18). Other measurements
In MESA, blood pressure was measured 3 times after the participant had rested in a seated position for 5 minutes using a Dinamap Pro 1000 automated oscillometric sphygmomanometer (Critikon Company, Tampa, Florida) and an appropriatesized cuff. The average of the last 2 measurements was used in the analysis. In SESSA, blood pressure was measured twice consecutively on the right arm of the seated participant after the participant had emptied his bladder for urinalysis and had sat quietly for 5 minutes, using an automated oscillometric sphygmomanometer (BP-8800; Omron Colin, Tokyo, Japan) with an appropriate-sized cuff, and the average of the 2 measurements was used. In MESA, a central laboratory (University of Vermont, Burlington, Vermont) measured levels of total and high-density
Downloaded from http://aje.oxfordjournals.org/ at Library - Faculty of Medicine Ramathibodi Hospital on March 7, 2015
of increasing CHD incidence (3, 4), while the overall incidence of CHD in the United States is estimated to have declined in recent years (5–7). Given these changing trends between the United States and Japan, it is of interest to compare the CHD burden between the 2 countries by age group, because there may be graded relationships in CHD burden between the countries across age groups. To obtain a definite answer, one should wait to observe clinical CHD trends in the 2 populations over time, which is time-consuming and labor-intensive. In contrast, comparing subclinical measures of atherosclerosis affords investigators a unique opportunity to obtain insight into the burdens of coronary atherosclerosis. Coronary artery calcium (CAC) level is a well-documented marker for coronary atherosclerosis (8), and the Agatston score (9), a quantitative measure of CAC level, is shown to correlate well with autopsy-confirmed coronary artery plaque levels (10, 11). Therefore, comparison of CAC scores is likely to provide a better assessment of the overall burden of subclinical CHD than a focus on individual risk factors. We have previously shown that middle-aged Japanese men in Japan have a lower burden of CAC than Caucasian men in the United States, even after accounting for traditional risk factors (12). However, the age range of the samples was too narrow (40–49 years) to evaluate the difference by age group. In the present study, we compared community-based samples of men in a broader age range who were recruited from 6 study sites in the United States (the Multi-Ethnic Study of Atherosclerosis (MESA)) and 1 site in Japan (the Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA)). The objectives of the study were: 1) to compare CAC scores between Caucasian men in the United States and Japanese men in Japan, accounting for the different distributions of conventional coronary disease risk factors, and 2) to examine whether the magnitude of the difference in CAC between the 2 populations, if it exists, differed according to age group.
592 Fujiyoshi et al.
Statistical analysis
First, we conducted the following analyses separately according to 10-year age group (45–54, 55–64, and 65–74 years). Each group of participants was further divided into 4 categories according to the presence of the 5 conventional risk factors (number of risk factors = 0, 1, 2, or ≥3). We then calculated the crude prevalences of CAC scores less than 10, 10–
