Ferdous Karimizand

By Isaac Karimi, Danial Naseri and Ferdous Karimizand

Dietary cholesterol has been suggested as a cause of dyslipidemic atherosclerosis with scarce convincing evidence. A systematic review and a meta-analysis were conducted in MEDLINE (2004–2015) to screen randomized controlled trials (RCTs) that used cholesterol-fed rabbits as a model of atherosclerosis. A total of 32 RCTs (n = 1104 New Zealand rabbits; 4.37 ± 2.52 months old) reported lipid and lipoprotein outcomes following cholesterol intake (0.98 ± 0.67%) for a duration of 8.90 ± 7.26 weeks. Cholesterol intakes significantly raised combined lipid and lipoprotein outcomes (standardized mean difference) in a random-effect model by 5.618 (95% CI: 4.592, 6.644; P = 0.0001). The value of I2, heterogeneity, was 89.387%, indicating real variation. A subgroup analysis based on the duration and amount of cholesterol feeding in a mixed-effects analysis showed combined heterogeneous effects of 2.788 (95% CI: 2.333, 3.244; P = 0.000; Q = 112.206; df = 14) and 5.538 (95% CI: 4.613, 6.463; P = 0.000; Q = 31.622; df = 6), respectively. Random-effect meta-regression conducted using cholesterol moderator did not support causal effects of dietary cholesterol in inducing atherosclerosis, which may be due to significant publication bias. These high levels of heterogeneity among studies may decline fidelity of this animal model for translation of dyslipidemic atherosclerosis.

Part of the book: Lipoproteins