The Interplay of Sirtuin-1, LDL-Cholesterol, and HDL Function: A Randomized Controlled Trial Comparing the Effects of Energy Restriction and Atorvastatin on Women with Premature Coronary Artery Disease

Introduction: HDL function has gained prominence in the literature as there is a greater predictive capacity for risk in early coronary artery disease when compared to the traditional parameters. However, it is unclear how dietary energy restriction and atorvastatin influence HDL function.

Methods: A randomized controlled trial with 39 women with early CAD divided into three groups (n = 13): energy restriction (30% of VET), atorvastatin (80 mg), and control. Analyses of traditional biochemical markers (lipid and glucose profile), circulating Sirt-1, and HDL function (lipid composition, lipid transfer, and antioxidant capacity).

Results: Participants' mean age was 50.5 ± 3.8 years. Energy restriction increased Sirt-1 by 63.6 pg/mL (95%CI: 1.5-125.7; = 0.045) and reduced BMI by 0.8 kg/m (95%CI: -1.349--0.273; = 0.004) in a manner independent of other cardiometabolic factors. Atorvastatin reduced LDL-c by 40.0 mg/dL (95%CI: -69.910--10.1; = 0.010). Increased Sirt-1 and reduced BMI were independently associated with reduced phospholipid composition of HDL (respectively, β = -0.071; CI95%:-0.136--0.006; = 0.033; β = 7.486; CI95%:0.350-14.622; = 0.040). Reduction in BMI was associated with lower HDL-free cholesterol (β = 0.818; CI95%:0.044-1.593; = 0.039). LDL-c reduction by statins was associated with reduced maximal lipid peroxide production rate of HDL (β = 0.002; CI95%:0.000-0.003; = 0.022) and total conjugated diene generation (β = 0.001; CI95%:0.000-0.001; = 0.029).

Conclusion: This study showed that energy restriction and atorvastatin administration were associated with changes in lipid profile, serum Sirt-1 concentrations, and HDL function.