Hisayama Study Japan in Which the Cause of Death Was Defined by Postmortem Examination

Changes in TC levels in three examinations (1961, 1974 and 1988) in Hisayama town

Adapted from Fujishima [2001], with permission from Medical Review Co., Ltd.

250 200 150 100 50 0

^ *

50-59

60-69

70- Age

40-49

50-59

60-69

Male

1988

1974

-▲--

T T

-♦-

-♦-

--<T\

*

I I I

40-49 50-59 60-69 70- Age *p < 0.05 vs. 1961; Tp < 0.05 vs. 1961

40-49 50-59 60-69 70- Age *p < 0.05 vs. 1961; Tp < 0.05 vs. 1961

Fig.43

A series of studies on the population of Hisayama town (which is representative of average Japanese lifestyle) had high accuracy of defining the type of death, which was determined by postmortem examinations. The health of people in Hisayama town (Fukuoka Prefecture), >40 years old, was followed for 32 years, and the results were reported for four age groups. The average TC values increased progressively from the first (1961), to the second (1974) and third (1988) examinations (as it also did in the whole Japanese population).

Conclusion: TC values tended to increase slightly with age in women (40-69 years old), but not much in men.

Our comments: Although certain events are often discussed as the 'cause of death', the type of death event from circulatory diseases in this study was carefully defined for three major types, but there was little controlled evidence about the mechanisms causing each type of death. The small changes in TC over time may reflect gradual changes in food composition and life style over that time period.

Trends of mortality and morbidity from circulatory diseases in the three examinations - Hisayama Study

Data taken from Fujishima [2001].

Morbidity (%) Ischemic heart disease Cerebral infarction Cerebral hemorrhage Whole stroke

Mortality (%) Ischemic heart disease

Cerebral infarction

Cerebral hemorrhage

Whole stroke

Morbidity (%) Ischemic heart disease Cerebral infarction Cerebral hemorrhage Whole stroke

Mortality (%) Ischemic heart disease

Cerebral infarction

Cerebral hemorrhage

Whole stroke

-

*

-

l

i

*

-

1

i * ii

*

I

2 4 6 8 10 12 *p < 0.05 vs. first examination fp < 0.05 vs. second examination

2 4 6 8 10 12 *p < 0.05 vs. first examination fp < 0.05 vs. second examination

Mortality was summed in four 8-year periods and expressed as deaths per 1,000 people per year. The number of subjects of the 1st, 2nd and 3rd populations was 1,621, 2,053 and 2,649, respectively. The CHD mortality in men was positively correlated with Atherogenic Index [(TC-HDL-C)/HDL-C] (data not shown in the original report). During this period (1961-1988), average TC

values increased both in men and women, mortalities from cerebral infarction, cerebral bleeding and all stroke decreased significantly while that of CHD was unchanged.

Conclusion: The incidence of hypertension, the most important risk factor of cardiovascular diseases, decreased steadily from the 1st to the 3rd examination, but the decreasing rate of stroke incidence has been diminishing recently, and the incidence of CHD remained unchanged during this period. It is highly possible that the preventive effect of hypertension management is compensated for by the increasing metabolic anomalies such as hyperlipidemia and glucose intolerance (a part of the original summary was translated).

Our comments: Increase in TC values was not associated with increase in CHD death rates but was associated with decrease in incidence of stroke during the 30 years. Very low mortality from stroke in Okinawa prefecture, Japan (well known for their longevity) was suggested to be the major basis for their longevity, and it was associated with a high intake of pork after World War II (data not shown).

Relative risk of TC for cerebral infarction and its subtypes in Hisayama -32-year follow-up study

Data taken from Tanizaki et al. [2000].

Relative Risk a Total Lacunar Athero- Cardio cerebral infarction thrombotic embolic

Relative Risk a Total Lacunar Athero- Cardio cerebral infarction thrombotic embolic

Men, event

n =

144

n =

81

n = 29

n = 31

Age-adjusted RR

1.1

1.2

1.1

1.0

Multivariate RR

_b

_b

_b

_b

Women, event

n =

154

n =

86

n = 33

n = 25

Age-adjusted RR

1.1

1.2

1.4

0.6c

Multivariate RR

_b

_b

_b

0.8c

a Risk for an increase

of 1 mmol/l TC; b

TC was found not to be the risk factor; c p < 0.05.

This community-based, prospective cohort study in Hisayama, Japan, included men (n = 707) and women (n = 914) aged 40 years and over, who were followed for 32 years from their 1st examination in 1961 until 1994, and the cause of death was defined by postmortem examinations.

Conclusion: TC showed an inverse correlation with mortality from cardioem-bolic infarction only in women (p < 0.05).

Our comments: In Japan, the biomarker, TC, was not correlated with total cerebral infarction or its subtypes in men or in women, but TC correlated inversely with cardioembolic infarction. The 'Cholesterol Hypothesis' does not fit the deaths in Hisayama.

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