Age and Genetic Risk Score and Rates of Blood Lipid Changes in China

Blood lipids are the primary cause of atherosclerosis. However, little is known about relationships between rates of blood lipid changes and age and genetic risk.

To evaluate associations of blood lipid change rates with age and polygenic risk.

This cohort is from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China, which was established from 1998 to 2008. Participants were followed up until 2020 (mean [SD] follow-up, 13.8 [4.3] years) and received 4 repeated lipid measurements. Data analysis was performed from June to August 2022. A total of 47 691 participants with available genotype data were recruited, and 37 317 participants aged 18 years or older were included in the final analysis after excluding participants who were lost to follow-up or with major chronic diseases, and those without blood lipid measurements at baseline and any follow-up survey.

Age and polygenic risk scores based on 126 lipid-related genetic variants.

The estimated annual changes (EAC) of blood lipids in milligrams per deciliter.

This study evaluated 37 317 participants (mean [SD] age of 51.37 [10.82] years; 15 664 [41.98%] were male). The associations of EACs of blood lipids with age differed substantially between male and female participants. Male participants experienced declining change as they got older for total cholesterol (EAC, 0.34 [95% CI, 0.14 to 0.54] mg/dL for age <40 years vs 0.01 [95% CI, -0.11 to 0.13] mg/dL for age ≥60 years), triglyceride (EAC, 3.28 [95% CI, 2.50 to 4.07] mg/dL for age <40 years vs -1.70 [95% CI, -2.02 to -1.38] mg/dL for age ≥60 years), and low-density lipoprotein cholesterol (LDL-C) (EAC, 0.15 [95% CI, -0.02 to 0.32] mg/dL for age <40 years vs 0.01 [95% CI, -0.10 to 0.11] mg/dL for age ≥60 years). Female participants had inverse V-shaped associations and the greatest rate of change appeared in the age group of 40 to 49 years (EAC for total cholesterol, 1.33 [95% CI, 1.22 to 1.44] mg/dL; EAC for triglyceride, 2.28 [95% CI, 1.94 to 2.62] mg/dL; and EAC for LDL-C, 0.94 [95% CI, 0.84 to 1.03] mg/dL). Change in levels of blood lipids were also associated with polygenic risk. Participants at low polygenic risk tended to shift toward lower blood lipid levels, with EACs of -0.16 (95% CI, -0.25 to -0.07) mg/dL; -1.58 (95% CI, -1.78 to -1.37) mg/dL; and -0.13 (95% CI, -0.21 to -0.06) mg/dL for total cholesterol, triglyceride, and LDL-C, respectively. Participants with high polygenic risk had the greatest rates of change for total cholesterol, triglyceride, and LDL-C (EAC, 1.12 [95% CI, 1.03 to 1.21] mg/dL; EAC, 3.57 [95% CI, 3.24 to 3.91] mg/dL; and EAC, 0.73 [95% CI, 0.65 to 0.81] mg/dL, respectively). Similar patterns were also observed across sex and age groups.

In this cohort study, EACs of blood lipids were significantly associated with age and polygenic risk, suggesting that prevention strategies for lipids should focus on individuals with high genetic risk and in the critical age window.