Modern prevalence of the Fredrickson-Levy-Lees dyslipidemias: findings from the Very Large Database of Lipids and National Health and Nutrition Examination Survey

Abstract

Introduction: Five decades ago, Fredrickson, Levy, and Lees (FLL) qualitatively characterized clinical dyslipidemias with specific implications for cardiovascular and non-cardiovascular morbidity and mortality. They separated disorders of elevated cholesterol and triglycerides into five phenotypes (types I-V) based on their lipoprotein profile. Although clinicians generally consider them rare entities, modern FLL prevalence may be greater than previously reported. Material and methods: We performed a cross-sectional analysis in 5,272 participants from the 2011-2014 National Health and Nutrition Examination Survey and 128,506 participants from the Very Large Database of Lipids study with complete, fasting lipid profiles. We used a validated algorithm to define FLL phenotypes employing apolipoprotein B, total cholesterol, and triglycerides. Results: Overall prevalence of FLL phenotypes was 33.9%. FLL prevalence in the general population versus clinical lipid database was: type I (0.05 vs. 0.02%), type IIa (3.2 vs. 3.9%), type IIb (8.0 vs. 10.3%), type III (2.0 vs. 1.7%), type IV (20.5 vs. 24.1%), and type V (0.15 vs. 0.13%). Those aged 40-74 years had a higher overall prevalence compared to other age groups (p < 0.001) and men had overall higher prevalence than women (p < 0.001). Those with diabetes (51.6%) or obese BMI (49.0%) had higher prevalence of FLL phenotypes compared to those without diabetes (31.3%; p < 0.001) and normal BMI (18.3%; p < 0.001). Conclusions: FLL phenotypes are likely far more prevalent than appreciated in clinical practice, in part due to diabetes and obesity epidemics. Given the prognostic and therapeutic importance of these phenotypes, their identification becomes increasingly important in the era of precision medicine.

PoLA/CFPiP/PCS/PSLD/PSD/PSH guidelines on diagnosis and therapy of lipid disorders in Poland 2021

“…Some lipoproteins present in the blood (i.e., LDL, lipoprotein (a) (Lp(a)), very low-density lipoprotein (VLDL) remnants and chylomicron remnants) are involved in all stages of atherogenesis, contributing to development of atherosclerotic cardiovascular disease (ASCVD) [ 35 ]. Therefore, lipid disorders in the form of increased plasma/serum concentration of analytes reflecting or associated with elevated atherogenic lipoprotein concentration are long-time recognised cardiovascular risk factors, based on the results of a huge number of experimental, epidemiological, and clinical studies [ 36 ].…”

Genetic Architecture And Clinical Outcomes Of The Fredrickson-Levy-Lees Dyslipoproteinemias

“…Our study adds to the growing evidence that FLL dyslipoproteinemias are underrecognized in contemporary Western populations(3,4). We show that identification of combinations of lipid derangement – as initially conceived by Fredrickson and colleagues – allows for refinement of CAD risk, as seen with the type IIb pattern when traditional lipid parameters are controlled for.…”

“…The FLL type III phenotype was not associated with CAD in our study, in contrast to prior descriptions. As previously reported, the apoB-based scheme may be more sensitive and less specific for severe versions of type III dysbetalipoproteinemia in comparison to ultracentrifugation (4,41). Further, given that type III is reported to be a labile finding even among APOE-2/2 carriers and likely highly influenced by environmental exposures, follow-up time in our model may not accurately reflect total remnant cholesterol exposure.…”

“…Application to contemporary Western populations reveals a high prevalence of FLL dyslipoproteinemia with relationships to subclinical atherosclerosis (3,4). Associations with clinical outcomes in large contemporary cohorts are presently unknown.…”

The Genetic Basis of Hypertriglyceridemia

“…Palmar xanthomas are common [1,56]. The prevalence of FDBL may be up to 1-2% in the general population, but the condition is often undiagnosed [54,57].…”