Total cholesterol and mortality from ischemic heart disease and overall cardiovascular disease in Korean adults

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.

Figure 1

Age- and sex-adjusted HRs across 8 categories of baseline total cholesterol (TC) for CVD mortality. TC categories (<140, 140–159, 160–179, 180–199 [reference], 200–219, 220–239, 240–259, and ≥260 mg/dL). The midpoint was used as a representative value of each TC category, except both ends (131 and 276), for which the median was used. HRs and 95% CIs were calculated using Cox proportional hazard models stratified by baseline age (years: 40–44, 45–54, 55–64, 65–74, 75–80). CI = confidence interval, CVD = cardiovascular disease, HR = hazard ratio. To convert TC from mg/dL to mmol/L, multiply by 0.02586.

Figure 2

HRs for mortality from CVD and IHD using restrictive cubic spline analysis. Restricted cubic splines of total cholesterol with 3 knots (150, 190, and 230 mg/dL) and 190 mg/dL as a reference were used for individuals with total cholesterol values <350 mg/dL (n = 502,369). Hazard ratios and 95% CIs were calculated using Cox proportional hazards models stratified by baseline age (years: 40–44, 45–54, 55–64, 65–74, 75–80), after adjustment for age at baseline (continuous variable), smoking status, alcohol use, income status, physical activity, body mass index, systolic blood pressure, and fasting glucose levels. AMI = acute myocardial infarction, CI = confidence interval, CVD = cardiovascular diseases, HR = hazard ratio, IHD = ischemic heart disease. To convert cholesterol from mg/dL to mmol/L, multiply by 0.02586.

Figure 3

HRs per each 39 mg/dL (1 mmol/L) increase in total cholesterol (TC), according to TC range. ^∗HRs and 95% CIs were calculated using Cox proportional hazard models stratified by baseline age (years: 40–44, 45–54, 55–64, 65–74, 75–80), after adjustment for the same variables as in Figure 2. The same abbreviations are used as in Figure 2. To convert glucose from mg/dL to mmol/L, multiply by 0.02586.

Figure 4

HRs for CVD mortality using restrictive cubic spline analysis according to sex, age, and systolic blood pressure. The same methods and abbreviations are used as in Figure 2. To convert cholesterol from mg/dL to mmol/L, multiply by 0.02586.

Figure 5

HRs for IHD mortality using restrictive cubic spline analysis according to sex, age, and systolic blood pressure. The same methods and abbreviations are used as in Figure 2. To convert cholesterol from mg/dL to mmol/L, multiply by 0.02586.

Figure 6

HRs for AMI mortality using restrictive cubic spline analysis according to sex, age, and systolic blood pressure. The same methods and abbreviations are used as in Figure 2. To convert cholesterol from mg/dL to mmol/L, multiply by 0.02586.