How are lipids affected in Down syndrome?

From the Guidelines

Down syndrome significantly impacts lipid metabolism, leading to abnormal lipid profiles characterized by higher triglycerides, lower HDL cholesterol, and elevated total cholesterol and LDL cholesterol levels, thereby increasing the risk of cardiovascular disease. The most recent and highest quality study, 1, published in 2024, emphasizes the importance of lipid screening and management in individuals with Down syndrome. Key recommendations include:

• Lipid screening should be performed initially after optimizing glycemia and annually thereafter [ 1 ].
• Optimal goals are LDL cholesterol <100 mg/dL, HDL cholesterol >35 mg/dL, and triglycerides <150 mg/dL [ 1 ].
• Initial therapy for abnormal lipids should consist of optimizing glycemia and medical nutritional therapy to limit saturated fat intake to <7%, limit cholesterol to <200 mg/day, and avoid trans fats [ 1 ].
• If LDL cholesterol remains >130 mg/dL after 6 months of dietary intervention, initiate therapy with statin, with a goal of LDL <100 mg/dL, while ensuring reproductive counseling for individuals of childbearing age due to the potential teratogenic effects of statins [ 1 ].

These lipid abnormalities in Down syndrome are attributed to the extra genetic material from chromosome 21, which affects enzymes involved in lipid metabolism, as well as lifestyle factors such as reduced physical activity, dietary patterns, and higher rates of obesity. Thyroid dysfunction, more prevalent in Down syndrome, can further disrupt lipid metabolism. Management strategies, as outlined in the most recent guidelines [ 1 ], focus on dietary modifications, regular physical activity, and, when necessary, medication to normalize lipid levels and mitigate the risk of cardiovascular disease.

From the Research

Lipid Profile in Down Syndrome

• Individuals with Down syndrome (DS) have been found to have an unfavorable lipid profile, which may contribute to their increased risk of cardiovascular disease (CVD) 2, 3, 4.
• Studies have shown that people with DS tend to have higher levels of low-density lipoprotein (LDL) cholesterol, triglycerides, and lipoprotein(a) (Lp(a)), and lower levels of high-density lipoprotein (HDL) cholesterol 2, 3, 5.
• A meta-analysis of 15 studies found significant differences in total cholesterol, HDL-C, and triglycerides between individuals with DS and controls, with individuals with DS having less favorable lipid concentrations 4.

Specific Lipid Parameters

• LDL cholesterol: Higher in individuals with DS compared to controls 2, 3.
• Triglycerides: Higher in individuals with DS compared to controls 2, 3, 5, 4.
• HDL cholesterol: Lower in individuals with DS compared to controls 2, 3, 5, 4.
• Lp(a): Higher in individuals with DS compared to controls 2.

Implications for Cardiovascular Risk

• The unfavorable lipid profile in individuals with DS may contribute to their increased risk of CVD 2, 3, 4.
• Regular monitoring of lipid profiles, particularly triglycerides, in children with DS should be part of standard clinical care 6.
• The unique lipid profile in individuals with DS may require specific cut-offs for this population, considering the risk for ischemic heart and Alzheimer's diseases 4.