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twice as often as those who maintained Japanese traditions but preferred standard American diet [20,21]. These studies, which contradict the Cholesterol Hypothesis, have been largely ignored, in spite of having been published in a high profile peer-reviewed American journal. Thus, if the low rate of CHD among the Japanese has little to do with cholesterol levels and the low mortality is for other reasons, then the MONICA result for Japan are explained. This leaves only one discordant point in an otherwise apparently random scatter of points in the Monica results.

The relationship between cholesterol levels and mortality is actually both complex and fascinating and will the subject of Part II of this review.

FRAMINGHAM RISK SCORES Framingham is a small town near Boston, MA, and has been the site of a study involving a large number of its inhabitants. The study has been ongoing since 1950 and now even involves the children of the original cohort. Early results from this study had a major impact on the development of the Cholesterol Hypothesis. A commonly used graphical representation of the results regarding cholesterol and the incidence of CHD shows two curves where the percentage of participants with or without CHD is plotted against TC. Both curves rise from around 100-120 mg/dL TC, pass through maxima percentage at around 200-220 mg/dL, and decline to zero at 400 mg/dL except for a small bump at higher TC attributed to those with FH. The CHD patient’s (n = 193) curve is slightly displaced to higher TC compared to that of people without CHD (n = 1378). While believers in the Hypothesis point to the added risk associated with elevated TC reflected in the displaced curve, its can also be pointed out that the vast majority of patients with CHD had TC levels similar to participants without CHD, and that the added risk appeared marginal. What this often displayed plot fails to show is that the risk of overall

mortality associated with TC participants whose cholesterol TC there was an 11% increase

disappeared for men above age had decreased on its own (i.e. no in coronary and total mortality [22].

48. lipid

In addition, in a longer follow-up, for lowering treatment), for each 1% drop of

The Framingham study also gave rise to the so-called Framingham Risk Score, a risk estimate of having CHD during the next 10 years. This score is widely used in the office setting to assess an individual’s risk of CHD. If one looks at the way the score is calculated, as one gets older, age become by far the dominant factor with the importance of cholesterol dropping off dramatically with age until it becomes almost insignificant for men and makes only a slight contribution for women. This is in spite of the arterial exposure to TC and LDL obviously increases with age. This is not a picture of overwhelming support for the Hypothesis.

WHAT ARE THE REAL RISK FACTORS FOR ATHEROSCLEROSIS? If we use CAC as a surrogate for atherosclerosis, then given that there does not seem to be any connection with serum cholesterol or LDL, are there other traditional or non-traditional risk factors that correlate with plaque


Traditional risk factors that consistently






turn and

up as most important in studies of the extent of age [13,17,23,24]. However, when the correlation

between the Framingham 10-year risk score and the CAC score is examined, generally a very poor found. In one study, 20% of individuals with very low Framingham risk ( 9% 10-year risk) were in have advanced atherosclerosis as judged by their calcium scores [25]. This study also found that

correlation fact found the ability

is to of

the CAC score to predict advanced atherosclerosis was improved by adding obesity and physical inactivity to the traditional risk factors. But it appears likely being omitted. It is possible that this factor is chronic stress and depression.

family history of heart disease, that there is still a major factor is There is also growing evidence
















there is very good evidence that stress in general is very large study an attempt was made to identify the

a strong predictor of CHD and CHD events [29,30]. In one major potentially modifiable risk factors for a heart attack. It

was found that the major factors were a diabetes and psychological factors, all

particular of which

blood lipoprotein (apolipoprotein), smoking, had approximately equivalent importance

hypertension, [30]. Having

psychological by a factor of

factors ranked approximately equal to diabetes, both of 2 to 3, suggests that chronic stress and depression may

which increased be major factors

the not

risk of a heart attack seriously considered

in routine CHD risk assessment, especially in the office setting. Its omission may account of sets of risk factors such as the Framingham score to correlate with the extent determined by CAC.

for of

a part of the failure atherosclerosis as

International Health News

November 2007

Page 15

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