USA: Very low and very high levels of LDL-C are both linked to an increased risk of cardiovascular disease (CVD) mortality, says a recent study published in the Journal of the American Heart Association. Very low levels of LDL-C were also tied to high risks of stroke and all-cause mortality.
Very low low‐density lipoprotein cholesterol (LDL‐C) treatment targets are recommended for people at high CVD risk by the current cholesterol guidelines. Recent observational studies however have shown that very low LDL‐C levels may be associated with increased mortality and other adverse outcomes. There is a need to determine the association between LDL‐C levels and long‐term risk of overall and cardiovascular mortality among the U.S. general population.

Against the above background, Shuang Rong, Academy of Nutrition and Health, Wuhan University of Science and Technology, Wuhan, China, and colleagues aimed to evaluate the association between the LDL‐C levels and all‐cause and CVD mortality risk in a nationally representative cohort with up to 27 years of follow up in the general population.
A nationally representative sample of 14 035 adults aged 18 years or older were included, who participated in the National Health and Nutrition Examination Survey III 1988–1994. Categorization of LDL‐C levels was done into 6 categories: <70, 70–99.9, 100–129.9, 130–159.9, 160–189.9, and ≥190 mg/dL. By linking death records through December 31, 2015, deaths and underlying death causes were ascertained.
Based on the study, the researchers reported the following findings:
4458 deaths occurred including 1243 deaths from CVD during 304 025 person‐years of follow-up. At baseline, the mean age was 41.5 years and 51.9% were women.
Very low and very high levels of LDL‐C were associated with increased mortality.
After adjustment for age, sex, race and ethnicity, education, socioeconomic status, lifestyle factors, C‐reactive protein, body mass index, and other cardiovascular risk factors, individuals with LDL‐C<70 mg/dL, compared to those with LDL‐C 100–129.9 mg/dL, had HRs of 1.45 for all‐cause mortality, 1.60 for CVD mortality, and 4.04 for stroke‐specific mortality, but no increased risk of coronary heart disease mortality.
Compared with those with LDL‐C 100–129.9 mg/dL, individuals with LDL‐C≥190 mg/dL had HRs of 1.49 for CVD mortality, and 1.63 for coronary heart disease mortality, but no increased risk of stroke mortality.
The researchers conclude, "these findings showed the adverse outcomes of both very high and very low LDL‐C levels, providing a new light of lipid control in lifestyle and clinic."
"There is a need for further investigation to elucidate the optimal range of LDL‐C levels for CVD health in the general population," they wrote.
Reference:
Rong S, Li B, Chen L, Sun Y, Du Y, Liu B, Robinson JG, Bao W. Association of Low-Density Lipoprotein Cholesterol Levels with More than 20-Year Risk of Cardiovascular and All-Cause Mortality in the General Population. J Am Heart Assoc. 2022 Aug 2;11(15):e023690. doi: 10.1161/JAHA.121.023690. Epub 2022 Jul 29. PMID: 35904192.