Low serum XXXX and mortality. Which is the cause and which is the effect?

@entity1 @entity64 @entity66 @entity301 @entity5 @entity130 @entity409 @entity204 @entity165
BACKGROUND: Many studies have reported an association between a low or lowered blood total @entity165 (TC) level and subsequent nonatherosclerotic disease incidence or @entity204 . The question of whether low TC is a true risk factor or alternatively a consequence of occult disease at the time of TC measurement remains unsettled. To shed new light onto this problem, we analyzed TC change over a 6- year period (from exam 1 in 1965 through 1968 to exam 3 in 1971 through 1974) in relation to subsequent 16-year mortality in a cohort of Japanese American @entity1 . METHODS AND RESULTS: The study was based on 5941 @entity1 45 to 68 years of age without prior history of @entity301 , @entity64 , @entity5 , or @entity409 at exam 1 who also participated in exam 3 of the Honolulu Heart Program. The association of TC change with mortality end points was investigated with two different approaches (continuous and categorical TC change) with standard survival analysis techniques. Falling TC level was accompanied by a subsequent increased risk of @entity204 caused by some @entity5 (hemopoietic, esophageal, and prostate), noncardiovascular noncancer causes (particularly @entity409 ), and all causes. The risk-factor-adjusted rate of all-cause mortality was 30% higher (relative risk, 1.30; 95% CI, 1.06 to 1.59) among @entity1 with a decline from middle (180 to 239 mg/dL) to low (< 180 mg/dL) TC than in @entity1 remaining at a stable middle level. By contrast, there was no significant increase in all-cause mortality risk among cohort @entity1 with stable low TC levels. Nonillness mortality ( @entity204 caused by @entity130 and suicide) was not related to either TC change or the average of TC levels in exams 1 and 3. CONCLUSIONS: These results add strength to the reverse-causality proposition that @entity66 cause TC to decrease.
