Cardiovascular disease prevention in heterozygous familial hypercholesterolemia: how important is a healthy diet in the era of long-lasting cholesterol-lowering drug therapies?

PURPOSE OF REVIEW: This review aims to provide an in-depth perspective on the importance of diet for cardiovascular disease (CVD) prevention in heterozygous familial hypercholesterolemia (HeFH). RECENT FINDINGS: Even though data on diet and CVD prevention in HeFH are limited, the currently available evidence supports its cholesterol-lowering effect and its favorable association with CVD risk on the long-term. However, qualitative evidence from individuals with HeFH suggests that there is a common perception that diet is useless compared to medication, and this misconception serves as a barrier to healthy eating. On the other hand, evidence also suggests that individuals with HeFH are at higher risk of eating disorders compared with unaffected individuals. Family history of premature death and the chronic nature of the disease would be in cause. SUMMARY: Emphasizing a healthy diet needs to remain at the foundation of CVD prevention in HeFH. Evidence are limited but supportive of the cholesterol-lowering and cardioprotective potential effects of diet. Engaging in conversations about healthy dieting with individuals in HeFH is likely to help prevent misconceptions about diet. Additionally, it could help reduce the risk of eating disorders, which, altogether, is likely to improve overall CVD prevention.

Relationship between lifestyle habits and cardiovascular risk factors in familial hypercholesterolemia.

BACKGROUND AND AIM: Little is known about the cardioprotective potential of a healthy lifestyle in familial hypercholesterolemia (FH). The objective of this study was to evaluate the relationship between lifestyle and cardiovascular risk factors in adults with FH. METHODS AND RESULTS: This cross-sectional study leveraged data from the CARTaGENE Quebec population-based cohort (Canada). Participants with FH were identified using the validated Simplified Canadian Definition for FH. A healthy lifestyle score (HLS), ranging from 0 to 5, was calculated per adherence to 5 lifestyle habits: 1) not smoking; 2) being physically active (≥150 min/week of moderate or vigorous physical activity); 3) eating a healthy diet (Alternate Healthy Eating Index ≥50%); 4) having a light to moderate alcohol consumption (men: 1-30 g/day; women: 1-15 g/day); and 5) sleeping 7-8 h/day. Among the 122 included individuals (women, n = 78; men, n = 44; mean age ± SD: 57.3 ± 6.7 years), 92 (75.4%) had a HLS ≤3/5, while only 5 (4.1%) had a HLS of 5/5. After adjustments for sex, age, body mass index, and lipid-lowering medication use, we found no evidence of an association between the HLS and concentrations of LDL-cholesterol (ß = 0.04, 95% CI = -0.08, 0.15 mmol/L; P = 0.54). However, the HLS was favorably associated with HbA1c levels (ß = -0.07, 95% CI = -0.13, -0.01%; P = 0.02), and statistical trends suggested favorable associations with HDL-cholesterol (ß = 0.06, 95% CI = -0.02, 0.14 mmol/L; P = 0.06) and waist circumference (ß = -2.22, 95% CI = -4.62, 0.17 cm; P = 0.07). CONCLUSION: This study suggests that a healthy lifestyle is favorably associated with CVD risk factors in adults with FH.

Warming in the land of the midnight sun: breeding birds may suffer greater heat stress at high- versus low-Arctic sites.

Rising global temperatures are expected to increase reproductive costs for wildlife as greater thermoregulatory demands interfere with reproductive activities. However, predicting the temperatures at which reproductive performance is negatively impacted remains a significant hurdle. Using a thermoregulatory polygon approach, we derived a reproductive threshold temperature for an Arctic songbird-the snow bunting (Plectrophenax nivalis). We defined this threshold as the temperature at which individuals must reduce activity to suboptimal levels (i.e. less than four-time basal metabolic rate) to sustain nestling provisioning and avoid overheating. We then compared this threshold to operative temperatures recorded at high (82° N) and low (64° N) Arctic sites to estimate how heat constraints translate into site-specific impacts on sustained activity level. We predict buntings would become behaviourally constrained at operative temperatures above 11.7°C, whereupon they must reduce provisioning rates to avoid overheating. Low-Arctic sites had larger fluctuations in solar radiation, consistently producing daily periods when operative temperatures exceeded 11.7°C. However, high-latitude birds faced entire, consecutive days when parents would be unable to sustain required provisioning rates. These data indicate that Arctic warming is probably already disrupting the breeding performance of cold-specialist birds and suggests counterintuitive and severe negative impacts of warming at higher latitude breeding locations.

Influence of the LDL-Receptor Genotype on Statin Response in Heterozygous Familial Hypercholesterolemia: Insights From the Canadian FH Registry.

BACKGROUND: Whether low-density lipoprotein (LDL) receptor (LDLR) residual activity influences the LDL-lowering effect of statins in heterozygous familial hypercholesterolemia (HeFH) remains unclear. The objective of this study was to investigate the relationship between the LDLR genotype and statin-induced LDL cholesterol (LDL-C) reductions in HeFH. METHODS: A total of 615 individuals with HeFH (receptor-defective [RD] genotype: n = 226; receptor-negative [RN] genotype: n = 389) from 7 lipid clinics across Canada who initiated statin monotherapy were included in this retrospective longitudinal study. Statin-induced reductions in LDL-C among individuals with RD and RN genotypes were compared with the use of linear models. RESULTS: There were 334 women and 281 men with a mean untreated LDL-C concentrations of 6.97 ± 1.65 mmol/L. Untreated and on-statin LDL-C levels where higher among patients with an RN genotype: untreated: RN 7.24 (95% confidence interval [CI] 6.98-7.50) mmol/L vs RD 6.70 (95% CI 6.41-6.98) mmol/L (P = 0.0002); on-statin: RN 4.50 (95% CI 4.31-4.70) vs RD 4.05 (95% CI 3.84-4.26) mmol/L (P = 0.0004). After adjustments for age, sex, smoking status, untreated LDL-C concentrations, statin type and dose, as well as the clinic where the patients were treated, the LDL-C-lowering effect of statins was significantly weaker for individuals with an RN mutation than for individuals with an RD mutation: RN: -31.1% (95% CI -34.7% to -27.4) vs RD -36.5% (95% CI -40.4% to -32.6%); P < 0.0001. The LDLR genotype was the strongest nonmodifiable independent correlate of statin-induced LDL-C reductions (R2 = 2.3%; P = 0.0001). CONCLUSION: The LDLR genotype is significantly associated with statin-induced reductions in LDL-C concentrations in HeFH.

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

BACKGROUND: Conclusive data on the effectiveness of dietary interventions in heterozygous familial hypercholesterolemia (HeFH) management are unavailable. Whether this is due to a true lack of effects or biases in intervention designs remains unsettled. We systematically assessed the impact on LDL-C of published dietary randomized controlled trials (RCTs) conducted among individuals with HeFH in relation to their design and risk of bias. METHODS: We systematically searched PubMed, Web of Science, and Embase in November 2020 to identify RCTs that assessed the impact of: (1) food-based interventions; (2) dietary counseling interventions; or (3) dietary supplements on LDL-C in individuals with HeFH. We evaluated the risk of bias of each study using the Cochrane Risk of Bias 2 method. RESULTS: A total of 19 RCTs comprising 837 individuals with HeFH were included. Of those, five were food-based interventions, three were dietary counseling interventions and 12 were dietary supplement-based interventions (omega-3, n = 3; phytosterols, n = 7; guar gum, n = 1; policosanol, n = 1). One study qualified both as a food-based intervention and as a dietary supplement intervention due to its factorial design. A significant reduction in LDL-C levels was reported in 10 RCTs, including eight dietary supplement interventions (phytosterols, n = 6, omega-3, n = 1; guar gum, n = 1), one food-based intervention and one dietary counseling intervention. A total of 13 studies were judged to have some methodological biases in a way that substantially lowers confidence in the results. Studies at low risk of biases were more likely to report significant reductions in LDL-C concentrations, compared with studies at risk of bias (chi-square statistic: 5.49; p = 0.02). CONCLUSION: This systemic review shows that the apparent lack of effectiveness of diet manipulation in modulating plasma levels of LDL-C among individuals with HeFH is likely due to biases in study designs, rather than a true lack of effects. The likelihood of reporting significant reductions in LDL-C was associated with the concurrent risk of bias.

Recognition errors by honey bee (Apis mellifera) guards demonstrate overlapping cues in conspecific recognition.

Honey bee (Apis mellifera) entrance guards discriminate nestmates from intruders. We tested the hypothesis that the recognition cues between nestmate bees and intruder bees overlap by comparing their acceptances with that of worker common wasps, Vespula vulgaris, by entrance guards. If recognition cues of nestmate and non-nestmate bees overlap, we would expect recognition errors. Conversely, we hypothesised that guards would not make errors in recognizing wasps because wasps and bees should have distinct, non-overlapping cues. We found both to be true. There was a negative correlation between errors in recognizing nestmates (error: reject nestmate) and nonnestmates (error: accept non-nestmate) bees such that when guards were likely to reject nestmates, they were less likely to accept a nonnestmate; conversely, when guards were likely to accept a non-nestmate, they were less likely to reject a nestmate. There was, however, no correlation between errors in the recognition of nestmate bees (error: reject nestmate) and wasps (error: accept wasp), demonstrating that guards were able to reject wasps categorically. Our results strongly support that overlapping cue distributions occur, resulting in errors and leading to adaptive shifts in guard acceptance thresholds.