Abstract

It is not completely clear whether "the lower, the better" cholesterol hypothesis for cardiovascular disease (CVD) and ischemic heart disease (IHD) can be applied to general populations with a low risk of heart disease mortality.We prospectively followed up 503,340 Koreans who participated in routine health checkups during 2002-2003 until 2013 via linkage to national mortality records.Nonlinear associations with total cholesterol (TC) were found: U-curves for overall CVD (I00-I99; nadir at 180-200 mg/dL) and a reverse-L-curve for IHD (I20-I25). Assuming a linear association in the lower range (<200 mg/dL), TC was inversely associated with CVD mortality (HR per 39 mg/dL [1 mmol/L] increase = 0.90). In the upper range (200-349 mg/dL), TC was positively associated with CVD mortality, largely due to IHD (HR = 1.19), especially acute myocardial infarction (HR = 1.23). The associations were generally similar in men versus women and in middle-aged (40-64 years) versus elderly (≥65 years) adults.TC levels of 180-200 mg/dL were associated with the lowest CVD mortality. Below 200 mg/dL, TC had no graded positive associations with IHD mortality. It remains unclear whether the lowest cholesterol levels are associated with the least mortality from CVD and IHD in Korean adults with a low risk of heart disease.

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