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. Author manuscript; available in PMC: 2019 Jul 26.
Published in final edited form as: J Hum Hypertens. 2003 Sep;17(9):631–639. doi: 10.1038/sj.jhh.1001606

Differences in cardiovascular disease risk factors between Japanese in Japan and Japanese-Americans in Hawaii: the INTERLIPID study

H Ueshima 1, A Okayama 2, S Saitoh 3, H Nakagawa 4, B Rodriguez 5, K Sakata 6, N Okuda 1, SR Choudhury 7, JD Curb, INTERLIPID Research Group5
PMCID: PMC6660154  NIHMSID: NIHMS1033139  PMID: 13679953

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.69 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.

Number of participants: four samples in Japan and Hawaii sample, INTERLIPID/INTERMAP 1997–1998, by gender and age

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.

Height, weight, and body mass index (BMI), systolic and diastolic blood pressures, treatment rate of hypertension, smoking and drinking rates, and sodium and potassium excretion in timed 24-h urine, in Japan and Hawaii, INTERLIPID, 1997–1998, by gender and age

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 24). 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.

Nutrient intake in Japan and Hawaii, average of 4 days of 24-h dietary recalls, INTERLIPID 1997–1998, by gender and age

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.

Serum lipids, uric acid, fibrinogen, and HbA1c in Japan and Hawaii, INTERLIPID 1997–1998, by gender and age

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.1618 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.1921 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.2,5,1621

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.

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