A new explanation has been published on engineering This paper highlights key findings from a large, multinational cohort study reevaluating cholesterol management for the prevention of cardiovascular and chronic diseases, suggesting a U-shaped association between cholesterol levels and mortality in Chinese adults, challenging the traditional “lower is better” approach. Although clinical guidelines have long prioritized lowering low-density lipoprotein cholesterol (LDL-C) as the cornerstone of primary prevention of atherosclerotic cardiovascular disease (CVD), emerging evidence shows an association between very low LDL-C and high cancer risk and suggests a U-shaped pattern between LDL-C and all-cause mortality, a discrepancy often confounded by lipid-lowering drugs and comorbidities.
This commentary, written by Jianxin Li and Xiangfeng Lu of Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, and Peking Union Medical College, summarizes a large prospective longitudinal study by Jiang et al. The study analyzed 163,115 Chinese adults and 317,305 British adults with a median follow-up of nearly 10 years, focusing on changes in untreated baseline cholesterol and long-term changes compared to all-cause and cause-specific mortality. This study revealed a U-shaped association between total cholesterol (TC), LDL-C, non-high-density lipoprotein cholesterol (HDL-C) and mortality in Chinese people by enrolling participants with severe chronic diseases and without lipid-lowering treatment to reduce reverse causation and confounding. High cholesterol was associated with increased mortality from coronary heart disease, and low cholesterol was associated with increased all-cause mortality and cancer mortality, particularly gastrointestinal and urinary system cancers. Very low levels, especially LDL-C below 70 mg·dL-¹ and TC below 120 mg·dL-¹, were associated with higher hemorrhagic stroke risk, independent of nutrition or obesity.
This study defined optimal cholesterol thresholds for Chinese adults as 200 mg dL−¹ for TC, 130 mg dL−¹ for LDL-C, and 155 mg dL−¹ for non-HDL-C, which are consistent with the guideline’s borderline high cutoff. Significant ethnic differences emerged: British adults had higher optimal thresholds of 250 mg dL-¹ for TC, 175 mg dL-¹ for LDL-C, and 200 mg dL-¹ for non-HDL-C, corresponding to guideline high cholesterol values. Unlike the U-shaped curve of the Chinese participants, the UK population showed an L-shaped dose-response curve, where elevated cholesterol was not associated with increased risk of death, likely due to higher baseline lipid levels, better management, overall health status, and genetic heterogeneity.
Long-term cholesterol changes also have prognostic value. Chinese adults with persistently low TC, LDL-C, or non-HDL-C, or whose levels decline from a baseline of low or intermediate levels, face higher all-cause mortality than those with stable intermediate levels, a pattern not seen in the UK group, likely due to sample limitations. These declines may indicate an underlying health condition such as aging, malnutrition, or frailty, and people with unexplained low or decreased cholesterol who are not receiving lipid-lowering therapy should be closely monitored.
The commentary points out the study’s strengths, including its diverse ethnic cohort of nearly 500,000 people, long follow-up, treatment-naïve participants, repeated measures, and comprehensive cholesterol and mortality analyses. Limitations include unclear sex-specific mortality effects and limited data on heterogeneity of genetic risk strata. The findings support population-tailored cholesterol strategies that balance cardiovascular benefits with cancer and mortality risks, moving beyond low, one-size-fits-all targets to precision management based on optimal population thresholds.
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Reference magazines:
Li, J., Lu, X. (2025). Optimization of cholesterol management strategies based on the association between cholesterol and mortality. engineering. DOI: 10.1016/j.eng.2025.10.004. https://www.sciencedirect.com/science/article/pii/S2095809925005983?via%3Dihub
