Abstract
Despite increase in serum total cholesterol, high smoking rate, and frequency of adverse blood pressure levels in Japan, coronary heart disease (CHD) incidence and mortality apparently remain substantially lower at all ages in Japan than in the US and other Western societies. To better understand these differences, we compared CHD biomedical risk factors and dietary variables in Japanese living in Japan and 3rd and 4th generation Japanese emigrants living a primarily Western lifestyle in Hawaii, in an ancillary study of the INTERMAP. Men and women aged 40–59 years were examined by common standardized methods—four samples in Japan (574 men, 571 women) and a Japanese-American sample in Hawaii (136 men, 131 women). Average systolic (SBP) and diastolic (DBP) blood pressures were significantly higher in men in Japan than in Hawaii; there were no significant differences in women. The treatment rate of hypertension was much lower in Japan than Hawaii. Smoking prevalence was higher, markedly so for men, in Japan than Hawaii. Body mass index, serum total and low-density lipoprotein cholesterol, HbA1c, and fibrinogen were significantly lower in Japan than in Hawaii; high-density lipoprotein cholesterol was higher in Japan. Total fat, saturated fatty acid intake, and Keys dietary lipid score were lower in Japan than in Hawaii. Polyunsaturated/saturated fatty acid ratio and omega-3 fatty acid intake were higher in Japan than in Hawaii. In conclusion, levels of several, especially lipid, CHD risk factors were generally lower in Japanese in Japan than in Japanese in Hawaii. These differences were smaller for women than men between Japan and Hawaii. They may partly explain lower CHD incidence and mortality in Japan than Western industrialized countries.
Keywords: blood pressure, coronary heart disease, diet, serum lipids, smoking, population study, Japanese, Japanese-Americans
Introduction
Dietary saturated fat and cholesterol have been demonstrated to cause increases in serum total cholesterol.1 The intake of these lipids has increased dramatically in Japan in recent decades, especially in the young.2,3 Thus, the mean serum total cholesterol of young and middle-aged Japanese in Japan appears to have reached levels similar to those of Americans.2,3 Throughout this period, average blood pressures and rates of hypertension have been at least as high in Japanese adults as among white Americans.4 In addition, although the smoking rate is declining steadily, Japanese men in Japan still have much higher smoking rates than men in Western societies.2,3 Nevertheless, coronary heart disease (CHD) incidence and mortality rates apparently remain substantially lower at all ages in Japan than in the US and other Western societies.2,3,5 It is important to elucidate reasons for this phenomenon.6–9 It is also of interest that differences in CHD morbidity and mortality are far smaller between women in Japan and in Western societies than those seen for men.2,3,5,9
To date, many comparisons of risk factor levels and rates of cardiovascular diseases between the Japanese in Japan and Western populations have been based on nonstandardized data. Differences in traditional as well as more recently described risk factors between the populations are often not well documented. To understand these differences better, we made standardized comparisons of CHD biomedical risk factors and dietary variables in Japanese living in Japan and 3rd and 4th generation Japanese emigrants living a primarily Western lifestyle in Hawaii.
Population samples and methods
In the INTERLIPID study, an ancillary study to the 17-sample 4-country INTERMAP study,10 574 men and 571 women aged 40–59 years in four centres in Japan, and 136 Japanese-American men and 131 Japanese-American women in the US sample in Honolulu, Hawaii were examined based on a standardized common protocol (Table 1). Methods of the INTERMAP study are reported elsewhere;10,11 a brief description is given here. Blood pressure measurements were made on four different days; medical and lifestyle information, four 24-h dietary recalls, and two 24-h urine collections were obtained per participant. For the INTERLIPID study, nonfasting blood was drawn, serum and plasma were centrifuged within 30 min of blood drawing, and stored immediately under refrigeration. All specimens were frozen and stored locally at − 70°C. Serum lipids, fibrinogen, HbA1c, and other variables were measured in a central laboratory approximately 6–12 months later. For these analyses, samples from Hawaii and the Japanese centres were shipped to the central laboratory in Japan on dry ice. Individual samples from the five centres were allocated for analyses randomly to avoid systematic measurement bias.
Table 1.
Centre | 40–49 years (n) | 50–59 years (n) | Total (n) | |
---|---|---|---|---|
Men | ||||
Japan | Hokkaido | 75 | 74 | 149 |
Toyama | 72 | 77 | 149 | |
Shiga | 68 | 62 | 130 | |
Wakayama | 73 | 73 | 146 | |
Total | 288 | 286 | 574 | |
Hawaii | 67 | 69 | 136 | |
Women | ||||
Japan | Hokkaido | 74 | 74 | 148 |
Toyama | 76 | 74 | 150 | |
Shiga | 66 | 63 | 129 | |
Wakayama | 75 | 69 | 144 | |
Total | 291 | 280 | 571 | |
Hawaii | 66 | 65 | 131 |
The central laboratory was standardized using the Lipid Standardization Program, Centers for Disease Control and Prevention, Atlanta, USA, and successfully met the criteria of precision and accuracy for control measurements.12 The laboratory is currently a member of the Cholesterol Reference Method Laboratory Network (CRMLN).13 Except for measurement of fibrinogen and HbA1c, serum was used and analysed by an autoanalyzer (Hitachi 7107). For fibrinogen concentration, the thrombin coagulation time method was used.14 HbA1c was measured by a high-perfusion liquid chromatography method standardized by the Japanese Diabetes Society.15
Results
Blood pressure
Both average systolic (SBP) and diastolic (DBP) blood pressures were significantly higher in men in Japan than in Hawaii (Table 2). No significant SBP or DBP differences were seen in women. The rate of hypertension treatment (defined as taking antihy-pertensive medication) was considerably lower for both men and women in Japan than Hawaii (P<0.01).
Table 2.
40–49 years |
50–59 years |
40–59 years |
|||||||
4 samples in Japan (288) Mean (s.d.) | Hawaii (67) Mean (s.d.) | 4 samples in Japan (286) Mean (s.d.) | Hawaii (69) Mean (s.d.) | 4 samples in Japan (574) Mean (s.d.) | Hawaii (136) Mean (s.d.) | ||||
Men | |||||||||
Body weight (kg) | 66.9 (9.0) | 78.2 (14.8) | P<0.001 | 66.8 (8.6) | 79.2 (15.1) | P<0.001 | 66.9 (8.8) | 78.7 (14.9) | P<0.001 |
Height (cm) | 168.8 (5.8) | 167.3 (l1.0) | P=0.059 | 167.1 (5.8) | 167.0 (5.9) | P=0.907 | 167.9 (5.8) | 167.1 (5.7) | P=0.156 |
Body mass index (kg/m2) | 23.5 (2.7) | 27.9 (4.9) | P<0.001 | 23.9 (2.7) | 28.3 (4.6) | P<0.001 | 23.7 (2.7) | 28.1 (4.7) | P<0.001 |
Systolic blood pressure (mmHg) | 119.5 (l3.0) | 117.2 (l1.0) | P=0.177 | 121.3 (13.1) | 118.7 (12.1) | P=0.134 | 120.4 (12.9) | 117.9 (11.6) | P=0.045 |
Diastolic blood pressure (mmHg) | 76.6 (10.3) | 74.2 (8.7) | P=0.076 | 77.0 (9.7) | 73.6 (8.2) | P=0.007 | 76.8 (10.0) | 73.9 (8.5) | P=0.002 |
Treatment rate of hypertension (%) | 2.8 | 17.9 | P<0.01 | 9.1 | 36.2 | P<0.01 | 5.9 | 27.2 | P<0.01 |
Smoking rate (%) | 56.6 | 16.4 | P<0.01 | 46.9 | 10.1 | P<0.01 | 51.7 | 13.2 | P<0.01 |
Drinking rate (%) | 97.2 | 65.7 | P<0.01 | 96.5 | 79.7 | P<0.01 | 96.9 | 72.8 | P<0.01 |
Sodium (mmol/day) in 24-h urine | 204.7 (53.9) | 174.5 (61.4) | P<0.001 | 216.5 (58.6) | 177.7 (55.5) | P<0.001 | 210.5 (56.6) | 176.1 (58.5) | P<0.001 |
Potassium (mmol/day) in 24-h urine | 48.4 (12.6) | 53.1 (17.1) | P=0.012 | 50.1 (13.9) | 52.9 (14.0) | P=0.128 | 49.2 (13.3) | 53.0 (15.6) | P=0.004 |
Sodium/potassium ratio in 24-h urine | 4.4 (1.2) | 3.5 (1.3) | P<0.001 | 4.5 (1.3) | 3.6 (1.4) | P<0.001 | 4.5 (1.3) | 3.6 (1.3) | P<0.001 |
40–49 years |
50–59 years |
40–59 years |
|||||||
4 samples in Japan (291) Mean (s.d.) | Hawaii (66) Mean (s.d.) | 4 samples in Japan (280) Mean (s.d.) | Hawaii (65) Mean (s.d.) | 4 samples in Japan (571) Mean (s.d.) | Hawaii (131) Mean (s.d.) | ||||
Women | |||||||||
Body weight (kg) | 56.2 (8.4) | 59.3 (10.1) | P=0.022 | 54.8 (7.6) | 62.7 (13.9) | P<0.001 | 55.5 (8.0) | 61.0 (12.2) | P<0.001 |
Height (cm) | 156.2 (5.6) | 152.8 (5.0) | P<0.001 | 153.3 (5.3) | 154.2 (4.5) | P=0.241 | 154.8 (5.6) | 153.5 (4.8) | P=0.007 |
Body mass index (kg/m2) | 23.0 (3.1) | 25.5 (4.8) | P<0.001 | 23.3 (3.0) | 26.4 (5.9) | P<0.001 | 23.2 (3.1) | 25.9 (5.4) | P<0.001 |
Systolic blood pressure (mmHg) | 112.0 (12.8) | 113.1 (12.4) | P=0.449 | 116.3 (14.7) | 118.2 (15.4) | P=0.358 | 114.1 (13.9) | 115.6 (14.1) | P=0.252 |
Diastolic blood pressure (mmHg) | 69.5 (9.5) | 69.7 (8.1) | P=0.899 | 71.5 (9.7) | 70.3 (8.9) | P=0.384 | 70.5 (9.6) | 70.0 (8.5) | P=0.602 |
Treatment rate of hypertension (%) | 2.4 | 15.2 | P<0.01 | 9.6 | 33.8 | P<0.01 | 6.5 | 24.4 | P<0.01 |
Smoking rate (%) | 11.7 | 9.1 | P<0.01 | 5.4 | 0.0 | P<0.01 | 8.6 | 4.6 | P<0.01 |
Drinking rate (%) | 82.1 | 40.9 | P<0.01 | 82.5 | 41.5 | P<0.01 | 82.3 | 41.2 | P<0.01 |
Sodium (mmol/day) in 24-h urine | 185.5 (54.9) | 128.6 (35.6) | P<0.001 | 186.6 (51.0) | 134.0 (48.6) | P<0.001 | 186.0 (53.1) | 131.3 (42.7) | P<0.001 |
Potassium (mmol/day) in 24-h urine | 47.2 (13.1) | 39.8 (9.8) | P<0.001 | 49.9 (14.5) | 44.1 (15.0) | P=0.004 | 48.5 (13.9) | 41.9 (12.9) | P<0.001 |
Sodium/potassium ratio in 24-h urine | 4.1 (1.18) | 3.4 (1.1) | P<0.001 | 4.0 (1.3) | 3.2 (1.0) | P<0.001 | 4.1 (1.2) | 3.3 (1.1) | P<0.001 |
Smoking and drinking
Japanese men in Japan had far higher smoking rates than Japanese-American men in Hawaii (P<0.01) (Table 2). While smoking rates were higher for women in Japan than Hawaii, differences were not as dramatic. Drinking rates for both men and women in Japan were also significantly higher than those in Hawaii.
Dietary and serum lipids, HbA1c, fibrinogen, dietary electrolytes
Body mass index (BMI) (kg/m2), total fat intake, intake of saturated, mono- and polyunsaturated fatty acids (% total kcal), serum total and low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), HbA1c, and fibrinogen were significantly lower in both men and women in Japan than in Hawaii (Tables 2–4). Omega-3 polyunsaturated fatty acid intake and the ratio of dietary polyunsaturated to saturated fatty acid intake (P/S) were significantly higher in Japan than in Hawaii (Table 4). However, cholesterol intakes were significantly higher in both men and women in Japan than in Hawaii (Table 4). Nevertheless, Keys dietary lipid score was significantly lower in men in Japan than in Hawaii. Mean levels of serum high-density lipoprotein cholesterol (HDL-C) were significantly higher in both men and women in Japan than in Hawaii (Table 3). Lp(a) concentration was not different between Japan and Hawaii. Sodium intakes were significantly higher in Japan than Hawaii for both men and women (Table 4). Vitamin A, β-carotene, calcium, magnesium, selenium, and iron intakes were significantly lower in both men and women in Japan than in Hawaii (Table 4).
Table 4.
40–49 years |
50–59 years |
40–59 years |
|||||||
4 samples in Japan (288) Mean (s.d.) | Hawaii (67) Mean (s.d.) | 4 samples in Japan (286) Mean (s.d.) | Hawaii (69) Mean (s.d.) | 4 samples in Japan (574) Mean (s.d.) | Hawaii (136) Mean (s.d) | ||||
Men | |||||||||
Energy (kcal/day) | 2,295.2 (462.1) | 2,516.2 (651.2) | P=0.010 | 2,260.0 (389.9) | 2,345.4 (588.0) | P=0.254 | 2,277.6 (427.7) | 2,429.6 (623.5) | P=0.008 |
Protein (g/day) | 88.4 (20.8) | 106.2 (33.2) | P<0.001 | 90.3 (19.3) | 99.7 (27.4) | P=0.008 | 89.3 (20.1) | 102.9 (30.4) | P<0.001 |
Fat (g/day) | 62.9 (l8.8) | 92.0 (31.0) | P<0.001 | 58.2 (15.9) | 85.6 (29.8) | P<0.001 | 60.6 (17.5) | 88.8 (30.4) | P<0.001 |
Saturated fatty acids (g/day) | 16.3 (5.7) | 27.8 (10.4) | P<0.001 | 14.8 (4.7) | 25.0 (9.5) | P<0.001 | 15.6 (5.3) | 26.4 (10.0) | P<0.001 |
Monounsaturated fatty acids (g/day) | 23.2 (7.6) | 35.2 (13.1) | P<0.001 | 20.8 (6.4) | 32.8 (12.5) | P<0.001 | 22.0 (7.1) | 34.0 (12.8) | P<0.001 |
Polyunsaturated fatty acids (g/day) | 16.0 (5.1) | 21.5 (7.2) | P<0.001 | 15.5 (4.8) | 20.7 (7.8) | P<0.001 | 15.8 (5.0) | 21.1 (7.5) | P<0.001 |
ω-3 fatty acids (g/day) | 3.4 (1.2) | 2.4 (0.9) | P<0.001 | 3.4 (1.2) | 2.3 (0.9) | P<0.001 | 3.4 (1.2) | 2.3 (0.9) | P<0.001 |
ω-6 fatty acids (g/day) | 12.6 (4.3) | 19.0 (6.5) | P<0.001 | 12.0 (4.0) | 18.3 (7.1) | P<0.001 | 12.3 (4.2) | 18.6 (6.8) | P<0.001 |
P/S ratio | 1.0 (0.3) | 0.8 (0.3) | P<0.001 | 1.1 (0.3) | 0.9 (0.3) | P<0.001 | 1.1 (0.3) | 0.8 (0.3) | P<0.001 |
Cholesterol (mg/day) | 455.6 (l78.2) | 324.5 (147.2) | P<0.001 | 436.0 (171.6) | 324.7 (145.9) | P<0.001 | 445.8 (175.1) | 324.6 (146.0) | P<0.001 |
Keys lipid score | 29.4 (5.8) | 32.4 (8.2) | P=0.006 | 28.0 (6.0) | 31.3 (7.7) | P=0.001 | 28.7 (5.9) | 31.8 (8.0) | P<0.001 |
Carbohydrate (g/day) | 296.9 (67.7) | 300.0 (80.7) | P=0.743 | 292.3 (65.4) | 273.9 (75.2) | P=0.042 | 294.6 (66.5) | 286.7 (78.8) | P=0.282 |
Dietary fibre (g/day) | 14.8 (4.7) | 19.4 (5.9) | P<0.001 | 16.1 (4.8) | 19.1 (7.5) | P=0.002 | 15.5 (4.8) | 19.3 (6.8) | P<0.001 |
Na (mg/day) | 4,992.1 (1,230.2) | 4,617.6 (1,444.9) | P=0.053 | 5,206.9 (1,398.9) | 4,300.0 (1,328.4) | P<0.001 | 5,099.1 (1,320.2) | 4,456.4 (1,391.0) | P<0.001 |
K (mg/day) | 2,813.0 (723.3) | 3,062.7 (956.3) | P=0.048 | 2,978.1 (713.1) | 3,073.3 (951.7) | P=0.438 | 2,895.3 (722.4) | 3,068.1 (950.4) | P=0.048 |
Ca (mg/day) | 573.9 (209.2) | 705.8 (362.7) | P=0.005 | 637.1 (233.7) | 603.8 (237.7) | P=0.290 | 605.4 (223.8) | 654.1 (308.9) | P=0.085 |
Mg (mg/day) | 283.1 (69.3) | 395.6 (146.9) | P<0.001 | 292.7 (67.2) | 383.7 (126.6) | P<0.001 | 287.9 (68.4) | 389.6 (136.6) | P<0.001 |
Se (μg/day) | 180.8 (70.4) | 177.0 (52.8) | P=0.684 | 201.0 (86.7) | 177.3 (61.0) | P=0.033 | 190.8 (79.5) | 177.2 (56.9) | P=0.021 |
Fe (mg/day) | 11.0 (2.9) | 20.5 (6.8) | P<0.001 | 11.8 (3.0) | 19.5 (5.7) | P<0.001 | 11.4 (3.0) | 20.0 (6.3) | P<0.001 |
P (mg/day) | 1,217.1 (292.9) | 1,437.3 (441.5) | P<0.001 | 1,246.6 (276.6) | 1,345.9 (384.6) | P=0.046 | 1,231.8 (285.0) | 1,390.9 (414.6) | P<0.001 |
Vitamin C (mg/day) | 120.1 (84.5) | 128.1 (83.2) | P=0.485 | 131.0 (76.1) | 130.6 (86.3) | P=0.969 | 125.6 (80.5) | 129.4 (84.5) | P=0.621 |
Vitamin A (IU/day) | 5,882.2 (3,810.1) | 9,690.0 (6,892.7) | P<0.001 | 6,494.9 (4,700.1) | 9,299.5 (5,751.8) | P<0.001 | 6,187.5 (4,284.0) | 9,491.9 (6,319.0) | P<0.001 |
Retinol (μg/day) | 415.8 (665.7) | 355.8 (379.1) | P=0.325 | 438.3 (1,084.9) | 315.2 (284.2) | P=0.351 | 427.0 (898.6) | 335.2 (333.7) | P=0.052 |
β-carotene (μg/day) | 2,697.8 (1,894.3) | 5,093.2 (4,014.5) | P<0.001 | 3,020.4 (1,931.0) | 4,940.7 (3,316.8) | P<0.001 | 2,858.6 (1,917.8) | 5,015.8 (3,664.2) | P<0.001 |
40–49 years |
50–59 years |
40–59 years |
|||||||
4 samples in Japan (291) Mean (s.d.) | Hawaii (66) Mean (s.d.) | 4 samples in Japan (280) Mean (s.d.) | Hawaii (65) Mean (s.d.) | 4 samples in Japan (571) Mean (s.d.) | Hawaii (131) Mean (s.d) | ||||
Women | |||||||||
Energy (kcal/day) | 1,844.6 (323.8) | 1,836.1 (418.5) | P=0.877 | 1,750.3 (319.4) | 1,745.3 (412.7) | P=0.927 | 1,798.4 (324.8) | 1,791.0 (416.6) | P=0.850 |
Protein (g/day) | 72.9 (15.3) | 73.2 (18.9) | P=0.902 | 71.1 (15.5) | 71.8 (20.0) | P=0.792 | 72.0 (15.4) | 72.5 (19.4) | P=0.786 |
Fat (g/day) | 56.8 (15.1) | 68.4 (23.8) | P<0.001 | 49.1 (13.4) | 63.6 (24.4) | P<0.001 | 53.0 (14.8) | 66.0 (24.1) | P<0.001 |
Saturated fatty acids (g/day) | 15.5 (5.1) | 20.9 (7.8) | P<0.001 | 13.2 (4.3) | 18.6 (7.1) | P<0.001 | 14.4 (4.9) | 19.7 (7.5) | P<0.001 |
Monounsaturated fatty acids (g/day) | 20.9 (6.1) | 26.0 (9.9) | P<0.001 | 17.4 (5.4) | 23.9 (11.1) | P<0.001 | 19.2 (6.0) | 25.0 (10.5) | P<0.001 |
Polyunsaturated fatty acids (g/day) | 14.0 (4.0) | 16.0 (6.1) | P=0.014 | 12.7 (3.6) | 15.9 (6.8) | P=0.001 | 13.4 (3.9) | 16.0 (6.4) | P<0.001 |
ω-3 fatty acids (g/day) | 2.8 (0.9) | 1.8 (0.7) | P<0.001 | 2.7 (0.9) | 1.9 (0.9) | P<0.001 | 2.7 (0.9) | 1.8 (0.8) | P<0.001 |
ω-6 fatty acids (g/day) | 11.2 (3.4) | 14.1 (5.5) | P<0.001 | 9.9 (3.1) | 14.0 (6.1) | P<0.001 | 10.6 (3.4) | 14.0 (5.8) | P<0.001 |
P/S ratio | 1.0 (0.3) | 0.8 (0.3) | P<0.001 | 1.0 (0.3) | 0.9 (0.4) | P=0.022 | 1.0 (0.3) | 0.9 (0.3) | P<0.001 |
Cholesterol (mg/day) | 383.3 (138.8) | 242.9 (105.4) | P<0.001 | 333.6 (134.3) | 242.6 (130.7) | P<0.001 | 358.9 (138.7) | 242.8 (118.2) | P<0.001 |
Keys lipid score | 32.3 (6.6) | 33.1 (8.4) | P=0.467 | 29.8 (6.2) | 31.1 (10.2) | P=0.296 | 31.1 (6.5) | 32.1 (9.4) | P=0.212 |
Carbohydrate (g/day) | 252.2 (50.5) | 229.1 (57.0) | P=0.001 | 249.9 (53.6) | 217.8 (59.2) | P<0.001 | 251.0 (52.0) | 223.5 (58.2) | P<0.001 |
Dietary fibre (g/day) | 15.3 (4.5) | 15.2 (5.8) | P=0.866 | 16.3 (5.0) | 16.2 (6.0) | P=0.857 | 15.8 (4.8) | 15.7 (5.9) | P=0.838 |
Na (mg/day) | 4,222.5 (1,095.2) | 3,299.2 (1,142.6) | P<0.001 | 4,177.3 (1,027.9) | 3,207.5 (1,022.5) | P<0.001 | 4,200.3 (1,062.0) | 3,253.7 (1,081.5) | P<0.001 |
K (mg/day) | 2,623.0 (637.4) | 2,325.0 (727.1) | P=0.001 | 2,734.9 (682.0) | 2,367.9 (637.3) | P<0.001 | 2,677.9 (661.5) | 2,346.3 (681.7) | P<0.001 |
Ca (mg/day) | 586.4 (210.2) | 545.9 (209.0) | P=0.158 | 628.1 (225.9) | 511.3 (176.6) | P<0.001 | 606.9 (218.8) | 528.8 (193.6) | P<0.001 |
Mg (mg/day) | 248.9 (56.0) | 278.2 (88.4) | P=0.012 | 251.1 (59.3) | 283.6 (88.4) | P=0.006 | 249.9 (57.6) | 280.9 (88.1) | P<0.001 |
Se (μg/day) | 150.1 (61.3) | 128.2 (42.0) | P=0.001 | 152.2 (65.8) | 123.3 (33.3) | P<0.001 | 151.2 (63.5) | 125.7 (37.8) | P<0.001 |
Fe (mg/day) | 9.9 (2.4) | 15.3 (4.7) | P<0.001 | 10.0 (2.6) | 15.1 (4.5) | P<0.001 | 9.9 (2.5) | 15.2 (4.6) | P<0.001 |
P (mg/day) | 1,040.8 (243.2) | 1,025.0 (248.6) | P=0.636 | 1,032.1 (243.7) | 994.0 (233.3) | P=0.253 | 1,036.5 (243.2) | 1,009.6 (240.7) | P=0.253 |
Vitamin C (mg/day) | 126.5 (72.1) | 101.7 (70.2) | P=0.012 | 137.1 (70.5) | 118.1 (72.7) | P=0.053 | 131.7 (71.4) | 109.9 (71.7) | P=0.002 |
Vitamin A (IU/day) | 5,901.6 (3,420.3) | 7,864.6 (5,206.6) | P=0.005 | 6,570.1 (3,986.0) | 9,419.6 (8,039.1) | P=0.007 | 6,229.4 (3,720.3) | 8,636.2 (6,780.9) | P<0.001 |
Retinol (μg/day) | 369.8 (501.0) | 275.9 (164.4) | P=0.009 | 266.0 (327.4) | 300.5 (403.3) | P=0.465 | 318.9 (427.6) | 288.1 (306.2) | P=0.339 |
β-carotene (mg/day) | 2,801.4 (1,839.0) | 4,159.6 (3,084.5) | P=0.001 | 3,410.1 (2,315.3) | 5,041.8 (4,871.9) | P=0.010 | 3,099.9 (2,106.5) | 4,597.4 (4,079.0) | P<0.001 |
P/S ratio: polyunsaturated/saturated fatty acids ratio.
Table 3.
40–49 years |
50–59 years |
40–59 years |
|||||||
4 samples in Japan (287) Mean (s.d.) | Hawaii (47) Mean (s.d.) | 4 samples in Japan (285) Mean (s.d.) | Hawaii (53) Mean (s.d.) | 4 samples in Japan (572) Mean (s.d.) | Hawaii (100) Mean (s.d.) | ||||
Men | |||||||||
Serum total cholesterol (mg/dl) | 200.1 (28.6) | 206.0 (30.5) | P=0.191 | 198.5 (29.0) | 213.1 (27.4) | P<0.001 | 199.3 (28.8) | 209.8 (29.0) | P<0.001 |
HDL-cholesterol (mg/dl) | 53.6 (l3.l) | 49.1 (10.6) | P=0.025 | 53.7 (14.2) | 51.2 (9.9) | P=0.111 | 53.7 (l3.7) | 50.2 (10.2) | P=0.003 |
LDL-cholesterol (mg/dl) | 122.0 (28.3) | 130.9 (28.9) | P=0.047 | 119.0 (28.7) | 136.9 (27.5) | P<0.001 | 120.5 (28.5) | 134.1 (28.2) | P<0.001 |
HDL-cholesterol/LDL-cholesterol | 0.471 (0.198) | 0.390 (0.110) | P<0.001 | 0.486 (0.216) | 0.389 (0.104) | P<0.001 | 0.479 (0.207) | 0.389 (0.106) | P<0.001 |
Triglyceride (geometric mean, mg/dl) | 135.9 (1.8) | 194.8 (1.8) | P<0.001 | 133.6 (1.8) | 198.3 (1.9) | P<0.001 | 134.8 (1.8) | 196.6 (1.8) | P<0.001 |
Lp (a) (geometric mean, mg/dl) | 8.5 (2.2) | 8.6 (2.7) | P=0.941 | 9.6 (2.3) | 8.7 (2.5) | P=0.410 | 9.0 (2.3) | 8.6 (2.6) | P=0.648 |
γ-GTP (geometric mean, U/l) | 42.8 (2.2) | 35.8 (1.8) | P=0.077 | 43.6 (2.2) | 38.4 (1.7) | P=0.155 | 43.2 (2.2) | 37.2 (1.8) | P=0.024 |
Uric acid (mg/dl) | 5.80 (1.18) | 5.99 (1.14) | P=0.316 | 5.83 (1.20) | 6.59 (1.17) | P<0.001 | 5.80 (1.20) | 6.30 (1.20) | P<0.001 |
HbA1c (%) | 4.72 (0.50) | 4.92 (0.85) | P=0.132 | 4.82 (0.60) | 5.08 (0.73) | P=0.006 | 4.80 (0.60) | 5.00 (0.80) | P=0.006 |
Fibrinogen (mg/dl) | 248.3 (71.6) | 288.9 (55.2) | P<0.001 | 259.0 (66.1) | 286.9 (60.4) | P=0.004 | 253.7 (69.0) | 287.8 (57.8) | P<0.001 |
40–49 years |
50–59 years |
40–59 years |
|||||||
4 samples in Japan (290) Mean (s.d.) | Hawaii (52) Mean (s.d.) | 4 samples in Japan (280) Mean (s.d.) | Hawaii (54) Mean (s.d.) | 4 samples in Japan (570) Mean (s.d.) | Hawaii (106) Mean (s.d.) | ||||
Women | |||||||||
Serum total cholesterol (mg/dl) | 194.7 (29.3) | 204.5 (30.6) | P=0.028 | 210.2 (30.6) | 218.2 (32.5) | P=0.082 | 202.3 (30.9) | 211.5 (32.2) | P=0.005 |
HDL-cholesterol (mg/dl) | 61.1 (14.7) | 57.0 (10.8) | P=0.056 | 58.9 (13.7) | 62.3 (14.8) | P=0.109 | 60.0 (14.2) | 59.7 (13.2) | P=0.810 |
LDL-cholesterol (mg/dl) | 117.2 (27.4) | 132.6 (30.3) | P<0.001 | 130.7 (30.9) | 141.3 (36.0) | P=0.048 | 123.8 (29.9) | 137.0 (33.5) | P<0.001 |
HDL-cholesterol/LDL-cholesterol | 0.560 (0.251) | 0.460 (0.170) | P<0.001 | 0.485 (0.204) | 0.492 (0.255) | P=0.845 | 0.523 (0.232) | 0.476 (0.217) | P=0.052 |
Triglyceride (geometric mean, mg/dl) | 89.2 (1.6) | 125.5 (1.7) | P<0.001 | 107.5 (1.6) | 151.2 (1.7) | P<0.001 | 97.8 (1.6) | 138.0 (1.7) | P<0.001 |
Lp (a) (geometric mean, mg/dl) | 9.5 (2.3) | 12.2 (2.3) | P=0.051 | 11.7 (2.4) | 12.4 (2.5) | P=0.644 | 10.5 (2.4) | 12.3 (2.4) | P=0.087 |
γ-GTP (geometric mean, U/l) | 16.9 (2.2) | 21.5 (1.8) | P=0.003 | 43.6 (2.2) | 38.4 (1.7) | P=0.002 | 43.2 (2.2) | 37.2 (1.8) | P<0.001 |
Uric acid (mg/dl) | 3.95 (0.90) | 4.43 (0.95) | P<0.001 | 4.38 (0.85) | 4.85 (1.38) | P=0.019 | 4.20 (0.90) | 4.60 (1.20) | P<0.001 |
HbA1c (%) | 4.52 (0.41) | 4.62 (0.44) | P=0.109 | 4.67 (0.46) | 4.87 (0.80) | P=0.078 | 4.60 (0.40) | 4.70 (0.70) | P=0.021 |
Fibrinogen (mg/dl) | 250.5 (63.6) | 308.8 (63.0) | P<0.001 | 267.0 (66.1) | 312.3 (58.7) | P<0.001 | 258.6 (65.3) | 310.6 (60.6) | P<0.001 |
Discussion
The main findings from this end-of-century survey of population samples of Japanese in Japan and Japanese-Americans in Honolulu, Hawaii aged 40–59 years are: for both men and women, more favourable levels of several dietary and blood lipid variables were observed in Japan than in Hawaii, that is, lower intake levels for total fat, SFAs, PFAs/SFAs, and lower serum total cholesterol, LDL-C, triglycerides; higher intake of omega-3 fatty acids, higher serum HDL-C, and lower BMI. HbA1c and fibrinogen levels were also more favourable (ie, lower) for both men and women in Japan than in Hawaii. In contrast, cigarette smoking rates were higher for Japanese than Japanese-Americans, as were average levels of SBP, DBP, and rates of hypertension for Japanese men than Japanese-American men. Rates of hypertension treatment were lower for Japanese than Japanese-Americans.
This pattern of contrasting findings for the traditional readily measured major CHD–CVD risk factors (serum cholesterol, SBP/DBP, cigarette smoking) and dietary neutral fats in middle-aged Japanese compared to Japanese-Americans (also, Americans generally) at the end of the 20th century is consistent with the results repeatedly reported during the latter half of the century, for example, by the Seven Countries and Ni-Hon-San studies.16–18 Given the extensive data showing that CHD rates have been much lower for Japan than the USA throughout this period, with the contrast especially marked for men (present but quantitatively less for women), and that this contrast remains conspicuous in the latest data, key theoretical inferences are self-evident. Among the established major risk factors, dietary lipids and the serum lipids they influence are critically important for the occurrence of epidemic CHD.19–21 When these are favourable in the whole population, the impact of other major risk factors (adverse SBP/DBP, cigarette smoking) on CHD risk is of limited expression. When these are adverse, the impact of each major risk factor is massive, especially in combination, producing full-blown epidemic CHD.2,5,16–21
In the present study, these differences in CHD risk factors were larger in men than in women. Thus, gender differences in CHD risk factors between the populations may contribute to apparent differences in CHD and stroke morbidity and mortality patterns on a population basis.2,3,5
BMI for Japanese men and women was lower than for Japanese-Americans. There was no difference in height for men or women between Japan and Hawaii. Among Japanese, obesity was much less common than among Japanese-Americans, especially among men. Thus in Japan, lean body mass, especially in men, may have contributed to lower CHD risk, that is, lower serum total cholesterol, LDL-C, triglycerides, HbA1c, and fibrinogen levels and higher HDL-C levels (despite much higher smoking rates) than those of Japanese-Americans in Hawaii. Lower serum total cholesterol and LDL-C levels in Japan are correlated with lower saturated fat and PFA/SFA intakes and Keys lipid score than those in Hawaii, and prevail despite higher dietary cholesterol intake in Japan, a development in recent decades, reflecting the encouragement of whole egg intake to improve protein nutrition. Preliminary data from INTERMAP indicate that the higher omega-3 fatty acid intake in Japanese is apparently related to higher fish intake.22 In Japan, those aged 40 years and older consume more than 100 g of fish daily,23 a general finding nationwide, also recorded in INTERMAP.22 The higher fish consumption in Japan may also relate to the lower serum total cholesterol, LDL-C, and triglycerides. In addition, data from Japanese participants in the Honolulu Heart Program—the fathers of the Hawaii population in the present study—indicate that fish consumption may be a protective factor against heart disease in smokers.24
Despite the higher per cent of calories from carbohydrate, and despite higher smoking rates for Japanese compared to Japanese-Americans, most conspicuously in men, HDL-C levels were higher in Japanese than in Japanese-Americans. This finding is related to the lower BMI of the Japanese, although there may be other factors involved as well, including a higher per cent of total calories from alcohol for the Japanese compared to the Japanese-Americans. Be all that as it may, these data refute the notion about a presumed problem with lower intake of per cent total calories from fat, and higher intake of per cent total calories from carbohydrate instead, that is, the claim that this dietary pattern is responsible for lower HDL-C. Chinese data from the PRC-USA co-operative study are consistent with our INTERLIPID findings.25
Blood pressure levels in Japanese men were higher than those in Japanese in Hawaii, despite lower body weight in Japan. This appears to be due principally to the large difference in the treatment rate of hypertension, which was much lower in Japan than in Hawaii. It may also relate to higher salt (NaCl) intake and higher dietary Na/K in Japanese than Japanese-Americans. We found similar phenomena in INTERSALT study samples in the late 1980s).26
In conclusion, levels of diet and blood lipid CHD risk factors (as well as BMI, HbA1c, fibrinogen) were generally lower in Japanese in Japan than in Japanese-Americans in Hawaii. In contrast, the smoking rate in Japan was much higher. In addition, there was a tendency for SBP/DBP and hypertension rates to be higher in Japan. All differences in CHD risk factors were larger in men than in women. Gender differences in CHD risk factors between the populations may help to explain known cross-population patterns of CHD and stroke morbidity and mortality. A better understanding of these differences in risk factor levels and their relationships to cardiovascular diseases in these societies can enhance the ability to cope more effectively with evolving lifestyles and lifestyle-related risk factor patterns, hence achieve greater success in preventing cardiovascular diseases in the 21st century.
Acknowledgements
This study was partly supported by the Ministry of Education, Science, Sports and Culture, Grant-in-Aid for Scientific Research (A), No. 090357003 in Japan and the Suntory Company; the Pacific Research Institute is supported by the Robert Perry Fund and the Hawaii Community Foundation. The INTERMAP Hawaii Center was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health (Grant 5-RO1-HL54868–03). The INTERMAP Study is supported by the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MA, USA (Grant 2-ROl-HL50490–06), as well as national and local agencies in the four countries. We express sincere thanks to Dr J Stamler for his useful comments on this paper.
INTERLIPID Study leadership:
Chairperson of INTERMAP in Japan: Hirotsugu Ueshima. Principal and co-principal investigators: S Saitoh, S Tanaka, K Shimamoto (Sapporo, Japan), H Nakagawa, K Miura, K Yoshita (Kanazawa), A Okayama, SR Choudhury, Y Kita (Shiga, Japan); T Hashimoto, K Sakata, S Morioka (Wakayama, Japan). Principal and co-principal investigators in Hawaii: JD Curb, B Rodriguez, K Masaki. National nutritionist, Japan: N Okuda. National conutritionist, Japan: K Yoshita. Research associates in Japan: T Isomatsu, T Takahashi, (Sapporo); Y Naruse, M Higashiyama (Kanazawa); T Kadowaki, M Watanabe, K Yamamoto, H Fuse, M Yoshioka, A Morino, Y Sekiya (Shiga); O Mohara, F Kinoshita, M Ohta, Y Shibe, K Oki (Wakayama). Local nutritionists: K Ishishita (Sapporo); K Yoshita (Kanazawa); A Morino, Y Sekiya (Shiga); Y Shibe, K Oki (Wakayama); J Lee (Honolulu). Management committee in Japan: H Ueshima, A Okayama, SR Choudhury, N Okuda, Y Kita. INTERMAP International Steering and Editorial Committee: J Stamler and P Elliott (Co-Chairs), B Dennis, AR Dyer, H Kesteloot, K Liu, R Stamler (deceased), H Ueshima, B Zhou.
References
- 1.Keys A, Anderson JT, Grande F. Serum cholesterol response to changes in the diet. Part I—III. Metabolism 1965; 14: 747–787. [DOI] [PubMed] [Google Scholar]
- 2.Ueshima H Trends in Asia, World wide trends, II. Global picture of CHD In: Marmot M, Elliott P (eds). Coronary Heart Disease Epidemiology. Oxford Press: Oxford, in press. [Google Scholar]
- 3.Ueshima H Changes in dietary habits, cardiovascular risk factors and mortality in Japan. Acta Cardiol 1990; 45: 311–327. [PubMed] [Google Scholar]
- 4.Baba S et al. Blood pressure levels, related factors, and hypertension control status of Japanese and Americans. J Hum Hypertens 1991; 5: 317–332. [PubMed] [Google Scholar]
- 5.Tunstall-Pedoe H et al. Contribution of trends in survival and coronary-event rates to changes in coronary heart disease mortality: 10-year results from 37 WHO MONICA project populations. Lancet 1999; 353: 1547–1557. [DOI] [PubMed] [Google Scholar]
- 6.Curb JD, Reed DM, Miller FD, Yano K. Health status and life style in elderly Japanese men with a long life expectancy. J Gerontol 1990; 45: S206–S211. [DOI] [PubMed] [Google Scholar]
- 7.Yano K et al. Plasma fibrinogen and its correlates in elderly Japanese men living in Japan and Hawaii. J Clin Epidemiol 1999; 52: 1201–1206. [DOI] [PubMed] [Google Scholar]
- 8.Kodama K, Sasaki H, Shimizu Y. Trend of coronary heart disease and its relationship to risk factors in a Japanese population: a 26-year follow-up, Hiroshima/Nagasaki study. Jpn Circ J 1990; 54: 414–421. [DOI] [PubMed] [Google Scholar]
- 9.Sekikawa A et al. Coronary heart disese mortality among men aged 35–44 years by prefecture in Japan in 1995–1999 compared with that among white men aged 35–44 by state in the United States in 1995–1998: vital statistics data in recent birth cohort. Jpn Circ J 2001; 65: 87–92. [DOI] [PubMed] [Google Scholar]
- 10.Stamler J et al. for the INTERMAP Research Group. INTERMAP: background, aims, design, methods, and descriptive statistics (non-dietary). J Human Hypertens 2003; 17: 591–608. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Dennis B et al. for the INTERMAP Research Group. INTERMAP: the dietary data—process and quality control. J Hum Hypertens 2003; 17: 609–622. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Nakamura M et al. The evaluation and the results of cooperative cholesterol and tryglyceride standardization program by WHO-CDC. Rinsho Byori 1982; 30: 325–332 (in Japanese). [PubMed] [Google Scholar]
- 13.Myers GL et al. Standardization of lipid and lipoprotein measurements In: Rifai N, Warnick GR, Dominiczak MH (eds). Handbook of Lipoprotein Testing. AACC: Washington DC, 1997, pp 223–250. [Google Scholar]
- 14.Hashimoto S Fibrinogen determination by thrombin time methods. Rinshou Byouri 1973; 21: 615–620 (in Japanese). [PubMed] [Google Scholar]
- 15.Shima K et al. Interlaboratory difference in HbA1c measurement in Japan. A report of the committee on interlaboratory standardization of HbA1c determination, the Japan Diabetes Society. Tounyou Byou 1994; 37: 855–864 (in Japanese with English abstract). [Google Scholar]
- 16.Keys A et al. The seven countries study: 2,289 deaths in 15 years. Prev Med 1984; 13: 141–154. [DOI] [PubMed] [Google Scholar]
- 17.Worth RM et al. Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California: mortality. Am J Epidemiol 1975; 102: 481–490. [DOI] [PubMed] [Google Scholar]
- 18.Robertson TL et al. Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California. Coronary heart disease risk factors in Japan and Hawaii. Am J Cardiol 1977; 39: 244–249. [DOI] [PubMed] [Google Scholar]
- 19.Stamler J et al. Low risk-factor profile and long-term cardiovascular and noncardiovascular mortality and life expectancy: findings for 5 large cohorts of young adult and middle-aged men and women. JAMA 1999; 282: 2068–2070. [DOI] [PubMed] [Google Scholar]
- 20.Stamler J et al. Serum cholesterol. Doing the right thing. Circulation 1993; 88: 1954–1960. [DOI] [PubMed] [Google Scholar]
- 21.Kesteloot H. Nutrition and health. Eur Heart J 1992; 13: 120–128. [DOI] [PubMed] [Google Scholar]
- 22.INTERMAP, Japan and INTERLIPID Research Group. A cooperative epidemiologic study on lifestyles related to prevention of hypertension: International study, INTERMAP. Report of INTERMAP, Japan and INTERLIPID, Department of Health Science, Shiga University of Medical Science, 2002. (in Japanese). [Google Scholar]
- 23.Research Group of Kenko-Eiyo. Results of National Nutrition Survey in 1998. Konumin-eiyo-no Genjyo. Daiichi Press: Tokyo, 2000. (in Japanese). [Google Scholar]
- 24.Rodriguez BL et al. Fish intake may limit the increase in risk of coronary heart disease morbidity and mortality among heavy smokers. The Honolulu Heart Program. Circulation 1996; 94: 2917–2923. [DOI] [PubMed] [Google Scholar]
- 25.Tao S et al. Serum lipids and their correlates in Chinese urban and rural populations of Beijing and Guangzhou. PRC-USA Cardiovascular and Cardiopulmonary Epidemiology Research Group. Int J Epidemiol 1992; 21: 893–903. [DOI] [PubMed] [Google Scholar]
- 26.The INTERSALT Co-operative Research Group. Appendix tables. Centre-specific results by age and sex. J Human Hypertens 1989; 3: 331–407. [PubMed] [Google Scholar]