IJE Advance Access originally published online on November 24, 2004
International Journal of Epidemiology 2005 34(1):173-179; doi:10.1093/ije/dyh285
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IJE vol.34 no.1 © International Epidemiological Association 2004; all rights reserved.
Cardiovascular Disease |
Much lower prevalence of coronary calcium detected by electron-beam computed tomography among men aged 40–49 in Japan than in the US, despite a less favorable profile of major risk factors
1 Department of Epidemiology, Graduate School of Pubic Health, University of Pittsburgh, Pittsburgh, USA
2 Department of Health Science, Shiga University of Medical Science, Otsu, Japan
3 Cardiovascular Institute, University of Pittsburgh, Pittsburgh, USA
4 Department of Internal Medicine: Endocrinology and Metabolism, Shiga University of Medical Science, Otsu, Japan
5 Medical Coordination Center, Shiga University of Medical Science, Japan
6 Department of Radiology, Shiga University of Medical Science, Japan
7 Department of Internal Medicine: Cardiology, Shiga University of Medical Science, Japan
Correspondence: Dr Akira Sekikawa, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 3512 Fifth Avenue, Pittsburgh, PA 15213, USA. E-mail: akira{at}pitt.edu
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Abstract |
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Background Since World War II (WWII), exposures to westernized lifestyle have occurred in many non-Western countries, including Japan. National surveys showed that risk factor profiles for atherosclerosis around 1990 were similar in men in the post WWII birth cohorts in the US and Japan. We compared the degree of coronary calcium and other factors in men in the post WWII birth cohort: men aged 40–49 in the US and Japan.
Methods We conducted a cross-sectional study examining randomly selected 100 men from Kusatsu, Japan, and 100 men from Allegheny County, US. Coronary calcium was assessed using electron-beam computed tomography.
Results Systolic blood pressure, total cholesterol, low density lipoprotein (LDL)-cholesterol, and smoking rates were higher among the Japanese (122.6 ± 14.1 versus 113.7 ± 9.6 mmHg, P < 0.01; 5.72 ± 0.90 versus 4.99 ± 0.81 mmol/l (220.9 ± 34.6 versus 192.8 ± 31.3 mg/dl), P < 0.01; 3.52 ± 1.01 versus 3.10 ± 0.78 mmol/l (136.0 ± 39.0 versus 119.7 ± 30.0 mg/dl), P < 0.01; and 48 versus 15%, P < 0.01, respectively). Triglycerides and fibrinogen were similar. High density lipoprotein (HDL)-cholesterol was higher among the Japanese. Body mass index, fasting insulin, and C-reactive protein were higher among the Americans. Prevalence of coronary artery calcium score >0 was strikingly lower among the Japanese than the Americans (13% versus 47%, P < 0.01).
Conclusions Much lower prevalence of coronary calcium despite a less favourable profile of many major independent risk factors in the Japanese might imply that there are strong protective factors against atherosclerosis in the Japanese. Further investigation is of critical importance.
Keywords Subclinical atherosclerosis, electron-beam computed tomography, US, Japan, epidemiology, risk factors, post World War II birth cohort, coronary calcium
Accepted 2 June 2004
Since World War II (WWII), exposures to westernized lifestyle have occurred in many non-Western countries, including Japan. Men born after WWII in Japan have undergone major changes in diet and other lifestyle factors, including heavy cigarette smoking, increase in the levels of total and low density lipoprotein cholesterol (LDL-C), increase in cholesterol intake in diet (which is higher than in the US), increase in body weight and obesity, substantial increase in alcohol consumption, and increase in western foods.1 Comparing the survey data from national representative samples around 1990, risk factor profiles for coronary heart disease (CHD): total cholesterol, and systolic and diastolic blood pressure, were very similar in men in the post WWII birth cohorts in the US and Japan, except for much higher prevalence of cigarette smoking in Japan and much higher prevalence of obesity in the US.2 We compared CHD mortality in men aged 35–44 between the US and Japan and found that CHD mortality in Japan is still considerably lower than in the US: 23.7/100 000 for the US and 8.7/100 000 for Japan.3 After careful review, the differences do not appear to be explained by differences in potential misclassification of causes of death.3 These observations imply that there may be important protective factors that reduce risk of CHD in Japan.
Differences in genetic factors are unlikely to fully explain the difference in CHD mortality because studies of Japanese migrants to the US clearly illustrated the increase in CHD morbidity and mortality in Japanese men in the US.4 Epidemiological investigations monitoring and comparing CHD morbidity and mortality in the post WWII birth cohorts, i.e. age <50, between the countries would be very important. Such studies are, however, practically impossible to conduct because incidence of CHD is too low in the post WWII birth cohort.
Electron-beam computed tomography (EBT) is a non-invasive method for defining subclinical atherosclerosis of coronary arteries and accurately quantifying coronary artery calcium.5 Calcification within the coronary arteries is highly correlated with the extent of atherosclerosis. Coronary artery calcification occurs in small amounts in the early lesions of atherosclerosis in the second and third decades of life.5 It is found frequently in advanced lesions and in older age.
The key question is ‘Do Japanese men in the post WWII birth cohort with similar risk factor profiles as men in the US have as much or less coronary atherosclerosis?’ In this study, we tested the null hypothesis that there is no difference in the prevalence of coronary artery calcium detected by EBT between men aged 40–49 in the US and Japan. We also compared the traditional risk factors and other factors between the two populations.
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Methods |
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Subjects
Participants were 40–49 years of age and residents in Allegheny County, Pennsylvania (PA) or Kusatsu City, Shiga, Japan. Exclusion criteria included: (1) clinical cardiovascular disease, (2) type 1 diabetes, (3) cancer except skin cancer in the past 2 years, (4) renal failure, and (5) genetic familial hyperlipidaemias.
In Kusatsu City, subjects were randomly selected using the Basic Residents' Register which has each resident's information on name, birth date, address, household, and other details. From the Register, 300 men aged 40–49 were randomly selected and were contacted consecutively via phone. Among 203 men contacted from May 2001 to December 2002, 100 men agreed to participate in the study and were examined. The rate of participation was 49%. Of these 100, two subjects were excluded in the current analyses because EBT images were not obtained appropriately.
In Allegheny County, PA, subjects were volunteers. In May 2002, the study was announced through the University of Pittsburgh Medical Center (UPMC) Health Plan with the eligibility criteria. The UMPC Health Plan is a major health care insurer in the area of Pittsburgh, covering the majority of University workers and students. From June to October 2002, 100 subjects participated in the study. Among them, 99 were Caucasians.
Informed consent was obtained from all participants. The study was approved by the Institutional Review Boards of Shiga University Medical Science, Otsu, Japan, and University of Pittsburgh, Pittsburgh, US.
Study protocol
Participants were instructed to abstain from food or drink beginning at 8 p.m. on the previous day. On the examination day, their body weight and height were measured while they were wearing light clothing without shoes. Body mass index (BMI) was calculated as weight (kg)/height squared (m2). Waist circumference was measured at the level of the umbilicus while participant was standing erect. Blood pressure was measured in the right arm of seated participants after the participant emptied his bladder and sat quietly for 5 minutes, using an appropriate-sized cuff, with a standard mercury sphygmomanometer. The average of two measurements of the first (systolic) and fifth (diastolic) Korotkoff sounds was used for the analysis.
Venipuncture was performed early in the clinic visit after a 12-hour fast. The serum was kept at room temperature for 45 minutes. The plasma was then stored on ice and centrifuged within 60 minutes. Multiple aliquots of plasma or serum were prepared and frozen at –70°C. Serum samples were shipped on dry ice to the Heinz Laboratory, Department of Epidemiology, University of Pittsburgh, to measure lipids, glucose, and insulin. Serum lipids were measured with the standardized methods according to the Centers for Disease Control and Prevention, including total cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides. LDL-C was estimated by the Friedewald equation.6 When the value of triglycerides exceeded 4.52 mmol/l (400 mg/dl), LDL-C was measured directly using an automated spectrophotometric assay, LDL Direct Liquid Select (Equal Diagnostics, Exton US). There were two such subjects at each site. Serum glucose was determined using the hexokinase–glucose 6-phosphate dehydrogenase enzymatic assay. Serum insulin was determined using radio immunoassay (Linco Research Inc., St Charles, US).
Samples were shipped on dry ice to the Laboratory for Clinical Biochemistry Research, University of Vermont, to measure C-reactive protein (CRP) and fibrinogen. CRP was measured by a calorimetric competitive enzyme-linked immunosorbent assay. Fibrinogen was measured in an automated clot-rate assay using the ST4 instrument (Diagnostica Stago, Parsippany, US).
A self-administered questionnaire was used to obtain information on demography, smoking habits, alcohol drinking, fish intake, and other factors. Alcohol drinking was assessed as whether a participant drinks beer, wine, liquor, or sake with the frequency of drinking. Frequency of fish intake was assessed as <1/week, 1/week, 2–4/week, or >4 times/week.
Electron-beam computed tomography (EBT)
The scanning was done using a GE-Imatron C150 Electron Beam Tomography scanner (GE Medical Systems, South San Francisco, US) at both sites. Scanners were calibrated regularly by technologists following a standardized protocol. Measures of water density [0 Hounsfield Unit (HU)], air (-1000 HU), and calcification (threshold 130 HU) were uniform in the two scanners.
Scanning was performed in a standardized protocol to obtain 30–40 contiguous 3 mm thick transverse images from the level of the aortic root to the apex of the heart. Images were obtained during maximal breath holding using ECG triggering so that each 100 m second exposure was obtained during the same phase of the cardiac cycle. The amount of radiation exposure received from the EBT procedure is approximately 0.7 rem to the chest. All scan data were saved to optical disc.
Readings of the scanning were done centrally at the Cardiovascular Institute, Pittsburgh, using a DICOM (Digital Imaging and Communications in Medicine) workstation and software by AccuImage (AccuImage Diagnostic Corporation, San Francisco, US). The software program implements the widely accepted Agatston scoring method.7 Coronary artery calcium was considered to be present when three contiguous pixels (area = 1 mm2) >130 HU were detected overlying the vessels of interest. A calcium score was then calculated for each region of interest by multiplying the area of all significant pixels by a grade number (1, 2, 3, 4) indicative of the peak computed tomography number (HU). The individual region of interest scores were then summed for a total coronary calcium score. The reading was evaluated by one trained radiology technician. The reproducibility of the EBT scans from this laboratory had an intraclass correlation of 0.99.8
Since the distribution of coronary calcium score was very skewed, the data were analysed in a categorical form. To calculate the prevalence of coronary calcium, two cut points were used: >0 as well as <10, and 
10.
Statistical analysis
Values are expressed as means ± standard deviation (SD) and were compared with the use of a two-sample t-test. Continuous variables that showed highly skewed distribution (CRP and triglycerides) were compared with the use of the Mann-Whitney U test, and values were expressed as median and inter-quartile range. Dichotomous data (prevalence of coronary artery calcium, cigarette smoking, alcohol drinking, and fish eating) were compared with the use of the 
2 statistics. All P-values were two-tailed. P-value <0.05 was considered as significant. SPSS software (release 11.5.0, SPSS Inc., Chicago, US) was used for all statistical analyses.
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Results |
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Comparison of the major independent risk factors between men in the US and Japan
Levels of many major independent risk factors were less favourable among the Japanese men than among the American men (Table 1). Levels of systolic blood pressure were significantly higher among the Japanese men by about 10 mmHg. Prevalence of hypertension defined as levels of systolic blood pressure
140 mmHg, or levels of diastolic blood pressure 90 mmHg, or on anti-hypertensive medication was 19.4% for the Japanese and 11.0% for the Americans. Levels of total cholesterol as well as LDL-C were significantly higher among the Japanese men by about 0.73 mmol/l (28 mg/dl) and 0.41 mmol/l (16 mg/dl), respectively. Prevalence of current cigarette smoking was substantially higher among the Japanese men. Levels of HDL-C, in contrast, were significantly higher among the Japanese men by about 0.23 mmol/l (9 mg/dl).
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Comparison of other factors between men in the US and Japan
Differences were observed in obesity, levels of insulin, CRP and glucose, and some lifestyle factors, which may relate to major independent risk factors or atherosclerosis (Table 1). Anthropometry data showed that the American men were much more obese and had greater waist circumferences. Levels of insulin as well as CRP were much higher among the American men. Levels of triglycerides as well as fibrinogen were similar between the two populations. Levels of glucose were significantly higher among the Japanese men by about 0.44 mmol/l (8 mg/dl). Prevalence of diabetes defined as levels of fasting blood sugar
6.0 mmol/l (126 mg/dl) or being on anti-diabetic medication was 2.0% for both the Japanese and the Americans. Almost one half of the Japanese men drank alcohol every day, while only a small percentage of the American men drank alcohol every day (46% versus 16%; P < 0.01). All the Japanese men ate fish twice a week or more, while only 17% of the American men did.
Prevalence of subclinical atherosclerosis detected by EBT in men in the US and Japan
Prevalence of coronary artery calcium score >0, or 10 was strikingly lower among the Japanese men than the American men. Prevalence of coronary calcium score >0 was 47% among the American men, which is very similar to other reports in men in this age group in the US, while it was only 13% among the Japanese men. Similarly, prevalence of coronary calcium score 10 was 26% among the American men, and it was only 5% among the Japanese men. Among the American men, four subjects had coronary calcium score 100, while only one subject did among the Japanese men (Figure 1).
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Comparison of major independent risk factors and other factors by the presence of coronary calcium in each population
Table 2 shows the comparison of factors by the presence of coronary calcium (coronary calcium score >0 versus coronary calcium score = 0) in the American men as well as in the Japanese men. The American men with coronary calcium score >0 had significantly higher levels of fasting glucose, BMI, and waist circumference than those with coronary calcium score = 0. Levels of total cholesterol, HDL-C, or LDL-C did not appear to be different between the two groups in the American men. The Japanese men with coronary calcium score >0 had higher levels of total cholesterol, LDL-C, CRP, fibrinogen, lower levels of HDL-C, and higher prevalence of cigarette smoking than those with coronary calcium score = 0, although most of the differences did not reach statistical significance, due to the small number of subjects. We did the same analyses using the cut-point of calcium score 10 (coronary calcium score
10 versus <10). The results were very similar with those in Table 2, except the differences in the levels of both systolic and diastolic blood pressure reached statistical significance in both the Americans and the Japanese.
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Discussion |
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We observed strikingly lower prevalence of coronary artery calcium among the Japanese men than the American men despite a less favourable profile of several major independent risk factors: levels of systolic blood pressure, total cholesterol, and LDL-C, and the rate of cigarette smoking. The reason for this striking difference is largely unknown. Much higher levels of HDL-C among the Japanese in part account for the difference. Observed differences in obesity, especially central obesity, alcohol consumption, and fish intake may to some extent account for the difference in atherosclerosis formation.
Plausible mechanisms of the association of central obesity with atherosclerosis include small dense LDL, low HDL-C, large VLDL, high triglycerides, high systolic blood pressure, glucose intolerance, elevated CRP, abnormal coagulation/fibrinolytic profile, impaired endothelial function, and others.9 Although levels of LDL-C were higher among the Japanese men, it is possible that the American men had a greater proportion of small dense LDL particles because they had much greater waist circumference and higher insulin levels.10
Higher levels of systolic blood pressure among the Japanese men and similar levels of triglycerides and fibrinogen in the two populations are inconsistent with the profile related to central obesity described above. The much higher alcohol consumption in the Japanese men may in part relate to higher levels of blood pressure.11 Much higher intake of salt among the Japanese than Americans in general also may be in part responsible for the higher systolic blood pressure.1,12 Similar levels of fibrinogen may be in part due to much higher prevalence of cigarette smoking among the Japanese men.
Much more frequent intake of alcohol among the Japanese than the Americans may in part relate to the lower prevalence of coronary calcium among the Japanese through the increase in HDL-C, reduction in blood clotting and platelet aggregation, increase in insulin sensitivity, and other mechanisms.13
The National Nutrition Survey in Japan showed that the Japanese eat more than 100 g of fish a day; men aged 40–49 eat fish about 120 g/day on average1. Average fish consumption in epidemiological studies examining its association with CHD in Western and some non-Western countries ranged from 14 g/day to 60 g/day.14,15 This substantially higher fish consumption in the Japanese may exert some protective mechanisms against atherosclerosis, such as increasing the particle size of LDL,16 or reducing the levels of CRP.17
Reported variation in cholesterol ester transfer protein polymorphisms may affect both HDL-C levels and atherosclerosis.18 Variations in lipoprotein size, distribution, and particle concentration are related to atherosclerosis and CHD, independent of lipid levels.18 These factors may be affected by genetic polymorphisms of enzymes such as lipoprotein lipase or hepatic lipase and may be influenced by certain environmental factors such as lack of exercise and diets leading to central obesity.19
Very high consumption of isoflavonoids from soy products in the Japanese in general may in part account for the difference,1,20 although we did not examine soy consumption in this study.
Varying ‘lag time’ between exposure to risk factors and disease occurrence is unlikely to explain the difference because levels of total cholesterol in this post WWII birth cohort of US Caucasian men and Japanese men in Japan were very similar in the 1970s.2 Prevalence of cigarette smoking in this birth cohort in Japan was already much higher than in the US in the 1980s.1,12
Various minimal numbers of pixels have been used in different studies for distinguishing true foci of calcium from noise, raging from one pixel to four adjacent pixels.8,21–24 We employed a conservative threshold in this study: three adjacent pixels in our study. We also measured coronary calcium using a calcium volume score,25 which has higher reproducibility between scans than coronary calcium score by Agatston methods. The correlation coefficient between a coronary calcium score and a calcium volume score was 0.997. Body size per se may possibly be related to increased prevalence of small lesions simply due to increased random scatter of the electron beam. If the prevalence of small lesions increases due to increased random scatter of the electron beam, there is a statistically significant positive correlation between a coronary calcium score and body mass index, especially when a coronary calcium score is <10. There was, however, no significant correlation between coronary calcium score and body mass index (correlation coefficient –0.26, P = 0.895).
Risk factor profiles of the examined population in Japan do not seem to be much different from those in the general population in Japan. The levels of total cholesterol and HDL-C as well as the rates of alcohol drinking and cigarette smoking in this population were very similar to the numbers reported from the National Nutrition Survey.1
There are several limitations of the study. First, the study was cross-sectional in design and we cannot establish a causal relationship. Second, the sample size of the study was too small to conduct robust multi-variable analyses. Third, the subjects in the Pittsburgh site were not randomly selected but volunteers. The results of the Pittsburgh site, therefore, cannot be generalized to the US population.
In this volunteer sample, however, the risk relationship should be similar with that in a randomly selected population, because it is highly unlikely that the participants of this study had previous knowledge of their own coronary calcium score. Based on the levels of total cholesterol and the prevalence of cigarette smoking, the participants could be somewhat healthier than a randomly selected population.26 If this is the case, the prevalence of coronary calcium in a randomly selected population would be higher and the difference in the prevalence of coronary calcium would be much greater. One population-based study in the US reported that the prevalence of coronary artery calcium among men aged 40–49 was 42%.21 Two studies in the US reported the prevalence among men in this age group who were either physician- or self-referred, was around 45%.22,23 It is, therefore, unlikely that the prevalence of coronary artery calcium in the study population is significantly different from that in a randomly selected population.
Much lower prevalence of coronary calcium, despite a less favourable profile of most major independent risk factors in the Japanese, might imply that there are strong protective factors against atherosclerosis in the Japanese. Further investigation by evaluating and comparing the extent and severity of subclinical atherosclerosis in these populations and its relation to various factors is of critical importance.
KEY MESSAGES
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Acknowledgments |
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This research is supported in part by grants (beginning grant-in-aid by the American Heart Association (0160512U), and R01 by the National Institutes of Health (HL068200-01A1) to Dr Akira Sekikawa, and grant-in-aid for scientific research to Dr Hirotsugu Ueshima by the Japanese Ministry of Education, Culture, Sports, Science and Technology ( (A): 13307016) ). We thank Janet Bonk and Jennifer Rush for the recruitment of the participant in the US, Rhobert E Evans and Beth Ann Hauth for the laboratory work at the Heinz Laboratory to measure the blood samples in the US and Japan, and Lori Givens for reading the images of EBT in the US and Japan. We also thank Shinji Inoue, Kazutaka Masuda, and Tatsuya Honda for conducting EBT examination in Japan.
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References |
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1 Ministry of Health and Welfare. National Nutrition Survey 1998. Tokyo: Daiichi Shuppan Publisher, 2000.
2 Sekikawa A, Horiuchi BY, Edmundowicz D et al. A ‘natural experiment’ in cardiovascular epidemiology in the early 21st century. Heart (British Cardiac Society) 2003; 89:255–7.
3 Sekikawa A, Okamura T, Kadowaki T et al. Electron-beam computed tomography for identification of high-risk persons in primary prevention of coronary heart disease in the United States and its implication for Japan. Nippon Koshu Eisei Zasshi—Jap J Public Health 2003; 50:183–93.
4 Worth RM, Kato H, Rhoads GG, Kagan K, Syme SL. Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California: mortality. Am J Epidemiol 1975; 102:481–90.
5 O'Rourke RA, Brundage BH, Froelicher VF et al. American College of Cardiology/American Heart Association Expert Consensus document on electron-beam computed tomography for the diagnosis and prognosis of coronary artery disease. Circulation 2000; 102:126–40.
6 Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18:499–502.[Abstract]
7 Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1990; 15:827–32.[Abstract]
8 Sutton-Tyrrell K, Kuller LH, Edmundowicz D et al. Usefulness of electron beam tomography to detect progression of coronary and aortic calcium in middle-aged women. Am J Cardiol 2001; 87:560–64.[CrossRef][Web of Science][Medline]
9 McFarlane SI, Banerji M, Sowers JR. Insulin resistance and cardiovascular disease. J Clin Endocrinol Metab 2001; 86:713–18.
10 Tchernof A, Lamarche B, Prud'Homme D et al. The dense LDL phenotype. Association with plasma lipoprotein levels, visceral obesity, and hyperinsulinemia in men. Diabetes Care 1996; 19:629–37.[Abstract]
11 Ueshima H, Ozawa H, Baba S et al. Alcohol drinking and high blood pressure: data from a 1980 national cardiovascular survey of Japan. J Clin Epidemiol 1992; 45:667–73.[CrossRef][Web of Science][Medline]
12 US Department of Health and Human Service. Third National Health and Nutrition Examination Survey, 1988–1994, NHANES III Laboratory Data File (CD-ROM) Public Use Data File Documentation Number 762000. Hyattsville, MD: Centers for Disease Control and Prevention, 1996.
13 Agarwal DP. Cardioprotective effects of light-moderate consumption of alcohol: a review of putative mecanisms. Alcohol Alcohol 2002; 37:409–15.
14 Yuan JM, Ross RK, Gao YT, Yu MC. Fish and shellfish consumption in relation to death from myocardial infarction among men in Shanghai, China. Am J Epidemiol 2001; 154:809–16.
15 Marckmann P, Gronbaek M. Fish consumption and coronary heart disease mortality. A systematic review of prospective cohort studies. Eur J Clin Nutr 1999; 53:585–90.[CrossRef][Web of Science][Medline]
16 Mori TA, Burke V, Puddey IB et al. Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. Am J Clin Nutr 2000; 71:1085–94.
17 Madsen T, Skou HA, Hansen VE et al. C-reactive protein, dietary n-3 fatty acids, and the extent of coronary artery disease. Am J Cardiol 2001; 88:1139–42.[CrossRef][Web of Science][Medline]
18 Hirano K, Yamashita S, Matsuzawa Y. Pros and cons of inhibiting cholesteryl ester transfer protein. Curr Opin Lipidol 2000; 11:589–96.[CrossRef][Web of Science][Medline]
19 Hokanson JE. Functional variants in the lipoprotein lipase gene and risk cardiovascular disease. Curr Opin Lipidol 1999; 10:393–99.[CrossRef][Web of Science][Medline]
20 Erdman JW Jr. Soy Protein and Cardiovascular Disease: A Statement for Healthcare Professionals From the Nutrition Committee of the AHA. Circulation 2000; 102:2555–59.
21 Kaufmann RB, Sheedy PF 2nd, Maher JE et al. Quantity of coronary artery calcium detected by electron beam computed tomography in asymptomatic subjects and angiographically studied patients. Mayo Clinic Proceed 1995; 70:223–32.[Abstract]
22 Janowitz WR, Agatston AS, Kaplan G, Viamonte M Jr. Differences in prevalence and extent of coronary artery calcium detected by ultrafast computed tomography in asymptomatic men and women. Am J Cardiol 1993; 72:247–54.[CrossRef][Web of Science][Medline]
23 Mielke CH, Shields P, Broemeling LD. Coronary artery calcium scores for men and women of a large asymptomatic population. CVD Prevention 1999; 2:194–98.
24 O'Malley PG, Jones DL, Feuerstein IM, Taylor AJ. Lack of Correlation between Psychological Factors and Subclinical Coronary Artery Disease. N Engl J Med 2000; 343:1298–304.
25 Callister TQ, Raggi P, Cooil B, Lippolis NJ, Russo DJ. Effect of HMG-CoA reductase inhibitors on coronary artery disease as assessed by electron-beam computed tomography. N Engl J Med 1998; 339:1972–78.
26 National Center for Health, Statistics. Health, United States 2002. With Chartbook on Trends in the Health of Americans. Hyattsvile, 2002.
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