Abstract

Background: Normal serum total cholesterol (TC) based on standard lab definitions is typically considered <200 mg/dL. However, normal TC levels do not indicate optimal levels of low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C), the two measures most associated with risk of atherosclerotic cardiovascular disease (ASCVD). Methods: This study included all adults ≥18 years of age in NHANES from 1999-2018 without ASCVD and with TC <200 mg/dL while not on lipid-lowering therapy (n = 11,843). We evaluated age-adjusted, survey-weighted prevalence of LDL-C ≥100 mg/dL or non-HDL-C ≥130 mg/dL in the total population and within subgroups. Results: Among adults with normal TC, half (95% CI 48.5-51.3%) had either LDL-C ≥100 mg/dL or non-HDL-C ≥130 mg/dL. Among all subgroups, the highest prevalence of elevated LDL-C or non-HDL-C was seen in adults with elevated triglycerides (85.5% [95% CI 80.0-91.0%] for those with triglycerides > 400 mg/dL and 67.0% [95% CI 64.0-69.9%] with 150-400 mg/dL) or metabolic syndrome (66.2%, 95% CI 63.2-69.1%). A higher prevalence of elevated LDL-C or non-HDL-C was also seen in adults who were male, 40-80 years of age, or of Hispanic ethnicity, as well as those with pre-diabetes, diabetes, or elevated body mass index (Table). Prevalence of elevated LDL-C or non-HDL-C was substantially lower with decreasing levels of TC, ranging from 37.4% (95% CI 36.0-38.8%) for adults with TC <190 mg/dL down to 0.2% (95% CI 0.0-0.5%) for adults with TC <150 mg/dL (Table). Conclusions: Among adults free of ASCVD with TC <200 mg/dL and not on lipid lowering therapy, half have elevated serum LDL-C or non-HDL-C. Current definitions of normal TC are therefore insufficient to identify ASCVD risk in the general population, particularly those with metabolic syndrome, elevated blood glucose or triglycerides, or increased body weight. Lower goals for normal TC and increased emphasis on non-HDL-C should be considered as part of public health measures for primary prevention.

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