The impact of overweight on lipid phenotype in different forms of dyslipidemia: a retrospective cohort study

Abstract

Purpose: Dyslipidemia plays a pivotal role in increasing cardiovascular risk. In clinical practice the misleading association between altered lipid profile and obesity is common, therefore genetically inherited dyslipidemias may not completely be addressed among patients with overweight. Thus, we aim to investigate the influence of overweight and obesity on the lipid phenotype in a cohort of patients with different forms of dyslipidemia.

Methods: A retrospective analysis was conducted on patients with dyslipidemia from 2015 to 2022. Patients were stratified in familial hypercholesterolemia (FH), familial combined hyperlipidemia (FCHL), non-familial hyperlipidemia or polygenic hypercholesterolemia (PH). Clinical characteristics and lipid profile were evaluated.

Results: Of the total of 798 patients, 361 were affected by non-familial hyperlipidemia (45.2%), while FCHL, FH and PH was described in 19.9%, 14.0% and 20.9% of patients, respectively. Overweight prevalence was higher in FCHL and non-familial hyperlipidemia patients than FH and PH patients. Subjects with overweight and obesity were independently associated with lower levels of high-density lipoprotein cholesterol (HDL-C) compared to patients with normal weight (52.4 and 46.0 vs 58.1, respectively; p < 0.0001); levels of triglycerides (TG) and non-HDL-C were higher in patients with overweight and obesity than patients with normal weight (257.3 and 290.9 vs 194.8, and 221.5 and 219.6 vs 210.1, p < 0.0001 and p = 0.01, respectively), while no differences were observed between patients with overweight and obesity.

Conclusion: While dyslipidemias can be influenced by various factors, an important determinant may lie in genetics, frequently acting as an underlying cause of altered lipid profiles, even in cases of overweight conditions.

Keywords: Familial dyslipidemias; Lipid phenotype; Obesity; Secondary dyslipidemias.

Fig. 1

Diagnosis-related lipid profile distributions within our study population. This box plot representation compares the lipid profiles — Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), and Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) —across four distinct diagnostic categories: Familial Combined Hyperlipidemia (FCHL), Familial Hypercholesterolemia (FH), Non-familial hyperlipidemia, and Polygenic Hypercholesterolemia (PH). Each box plot illustrates the median (central line), interquartile range (box limits), and the full range excluding outliers (whiskers) for each lipid measure. The unit of measure was milligram on deciliter (mg/dL)

Fig. 2

Cross-sectional multivariate analysis between lipid profile and gender, weight status and smoking habits. Each forest plot represents a different generalized multivariate model which was adjusted considering sex, age, BMI, and smoking habits as fixed factors and covariates. Each forest plot is completed with the p-value for included variables and * represents statistically significant differences. The value of lipid profile was reported as standardized mean for each factors and covariates. HDL-C high-density lipoprotein cholesterol, LDL-C low-density lipoprotein cholesterol, TC total cholesterol, TG triglycerides