Diet and Cardiovascular Disease Risk Among Individuals with Familial Hypercholesterolemia: Systematic Review and Meta-Analysis

Abstract

Background: Although a cholesterol-lowering diet and the addition of plant sterols and stanols are suggested for the lipid management of children and adults with familial hypercholesterolemia, there is limited evidence evaluating such interventions in this population. Objectives: To investigate the impact of cholesterol-lowering diet and other dietary interventions on the incidence or mortality of cardiovascular disease and lipid profile of patients with familial hypercholesterolemia. Search methods: Relevant trials were identified by searching US National Library of Medicine National Institutes of Health Metabolism Trials Register and clinicaltrials.gov.gr using the following terms: diet, dietary, plant sterols, stanols, omega-3 fatty acids, fiber and familial hypercholesterolemia. Selection criteria: Randomized controlled trials evaluating the effect of cholesterol-lowering diet or other dietary interventions in children and adults with familial hypercholesterolemia were included. Data collection and analysis: Two authors independently assessed the eligibility of the included trials and their bias risk and extracted the data which was independently verified by other colleagues. Results: A total of 17 trials were finally included, with a total of 376 participants across 8 comparison groups. The included trials had either a low or unclear bias risk for most of the assessed risk parameters. Cardiovascular incidence or mortality were not evaluated in any of the included trials. Among the planned comparisons regarding patients’ lipidemic profile, a significant difference was noticed for the following comparisons and outcomes: omega-3 fatty acids reduced triglycerides (mean difference (MD): −0.27 mmol/L, 95% confidence interval (CI): −0.47 to −0.07, p < 0.01) when compared with placebo. A non-significant trend towards a reduction in subjects’ total cholesterol (MD: −0.34, 95% CI: −0.68 to 0, mmol/L, p = 0.05) and low-density lipoprotein cholesterol (MD: −0.31, 95% CI: −0.61 to 0, mmol/L, p = 0.05) was noticed. In comparison with cholesterol-lowering diet, the additional consumption of plant stanols decreased total cholesterol (MD: −0.62 mmol/L, 95% CI: −1.13 to −0.11, p = 0.02) and low-density lipoprotein cholesterol (MD: −0.58 mmol/L, 95% CI: −1.08 to −0.09, p = 0.02). The same was by plant sterols (MD: −0.46 mmol/L, 95% CI: −0.76 to −0.17, p < 0.01 for cholesterol and MD: −0.45 mmol/L, 95% CI: −0.74 to −0.16, p < 0.01 for low-density lipoprotein cholesterol). No heterogeneity was noticed among the studies included in these analyses. Conclusions: Available trials confirm that the addition of plant sterols or stanols has a cholesterol-lowering effect on such individuals. On the other hand, supplementation with omega-3 fatty acids effectively reduces triglycerides and might have a role in lowering the cholesterol of patients with familial hypercholesterolemia. Additional studies are needed to investigate the efficacy of cholesterol-lowering diet or the addition of soya protein and dietary fibers to a cholesterol-lowering diet in patients with familial hypercholesterolemia.

Impact of Diet on Plasma Lipids in Individuals with Heterozygous Familial Hypercholesterolemia: A Systematic Review of Randomized Controlled Nutritional Studies

“…Notably, our work also highlighted that, in adequate study settings, diet appears to impact LDL-C and other plasma lipids similarly among individuals with HeFH than among non-FH individuals – a finding that corroborates observational data on the relationship between dietary intakes and plasma lipids in HeFH [ 5 , 39 , 40 ]. Indeed, six of the seven interventions on phytosterol (sterols and/or stanols) supplementation we reviewed reported significant reductions in LDL-C among individuals with HeFH, ranging from 5 to 15% [ 7 ]. These reductions are consistent with mean effects on LDL-C reported in meta-analyses on phytosterol supplementation interventions conducted among non-FH individuals [ 41 ].…”

“…Given the genetic nature of this disease, diet has traditionally been considered as a secondary therapy, with limited effectiveness relative to medication [ 1 , 5 ]. Even though the literature on diet in HeFH management remains limited, previous systematic reviews and meta-analyses of dietary interventions among individuals with HeFH suggested that no conclusions can be made about the effectiveness of diet in HeFH [ 6 , 7 ]. Still, none of the previous reviews thoroughly assessed the impact on plasma lipids of dietary interventions conducted in HeFH, in line with the intervention design per se [ 6 , 7 ].…”

“…Even though the literature on diet in HeFH management remains limited, previous systematic reviews and meta-analyses of dietary interventions among individuals with HeFH suggested that no conclusions can be made about the effectiveness of diet in HeFH [ 6 , 7 ]. Still, none of the previous reviews thoroughly assessed the impact on plasma lipids of dietary interventions conducted in HeFH, in line with the intervention design per se [ 6 , 7 ]. This element is critical to investigate, as food-based interventions, dietary counseling studies and dietary supplement trials are exposed to specific biases (e.g., food substitution effect [ 8 ], adherence to dietary advice [ 9 ] or compliance with supplementation protocol [ 10 ]) which are likely to have different, yet direct impacts on their effectiveness in modulating plasma lipids [ 11 ].…”

“…These potential issues need to be taken into consideration when interpreting results in order to adequately appreciate the role of diet in HeFH management, and orient future research in the field. In summary, whether the apparent lack of effectiveness of dietary interventions in modulating plasma lipids in HeFH is due to a true lack of effects or to interventions’ design and associated biases remains unsettled [ 6 , 7 ].…”

Familial hypercholesterolaemia and COVID-19: A two-hit scenario for endothelial dysfunction amenable to treatment

“…It is even possible that in the past the combination of high cholesterol and relative lack of food benefitted those who got bacterial infections and improved their survival. In modern times, however, the situation is quite the opposite, as a large proportion of undiagnosed HeFH patients (as subjects in the general population) are likely to follow an unhealthy lifestyle, which induces several proatherogenic changes in lipoproteins thereby further increasing their risk for developing premature ASCVD [ 13 ].…”