A total of 798 patients affected by dyslipidemia were recruited in this retrospective study. Out of them, 41.7% were men (333/798), with a median age of 54 years (IQR 43, 63). The median BMI was 25.0 kg/m2 (IQR 22.7, 28.3), 446 patients (55.9%) were non-smokers and 344 subjects (43.3%) had hypertension.

Table 1 reports the patients’ characteristics stratified according to their diagnosis in FH, FCHL, Non-familial hyperlipidemia or PH. Most of patients were affected by non-familial hyperlipidemia (361/798, 45.2%), while FCHL, FH and PH was described in 158 (19.9%), 112 (14.0%) and 167 (20.9%) patients respectively.

Patients with FCHL were significantly more likely to be male (p < 0.0001), whereas patients with FH, PH, and non-familial hyperlipidemia were significantly more likely to be female (p < 0.0001). Patients with FCHL were significantly older than patients affected by non-familial hyperlipidemia (p = 0.003).

Patients with overweight were 275 (34.5%), while patients affected by obesity were 132 (16.5%). A diagnosis of inherited dyslipidemias was possible in 150 (54.5%) of patients with overweight, in 58 (43.9%) of patients with obesity and in 229 (58.6%) patients with normal weight with p = 0.014.

The prevalence of overweight and obesity were higher in patients with FCHL and non-familial hyperlipidemia than patients with FH and PH (Table 1). We did not find statistically significant differences for smoke habits between the four diagnoses of dyslipidemia, although patients with FH had significant lower levels of SBP compared to FCHL subjects (p = 0.004) and they were less likely to be diagnosed with arterial hypertension than patients with FCHL and non-familial hyperlipidemia. Figure 1 shows the diagnosis-related lipid profile of our population.

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)

A cross-sectional multivariate analysis was conducted to investigate the different lipid phenotype according to gender, weight status and smoking habits (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

Male gender was significantly associated with lower levels of TC (256.0, IC 95% 249.7–262.2 vs 282.6, IC 95% 275.0–290.1; p < 0.0001), HDL-C (45.3, IC 95% 43.1–47.4 vs 59.1, IC 95% 56.5–61.7; p < 0.0001), LDL-C (173.1, IC 95% 166.5- 179.7 vs 191.9 IC 95% 184.3–199.5; p < 0.0001), non-HDL-C (210.7, IC 95% 204.7–216.7 vs 223.5, IC 95% 216.2–230,74; p < 0.0001) and higher levels of TG than female patients (306.8, IC 95% 282.4–331.2 vs 188.6, IC 95% 159.0–218.1; p < 0.0001); active smokers were independently associated with lower levels of HDL-C (49.9, IC 95% 46.9–53.0 vs 54.4, IC 95% 53.0–55.9; p = 0.009) and higher levels of TG (269.9, IC 95% 235.5–305.4 vs 225.5, IC 95% 209.0–241.9; p = 0.023) than non-smokers.

Finally, subjects with overweight and obesity were independently associated with lower levels of HDL-C compared to patients with normal weight (52.4, IC 95% 50.2–54.7 and 46.0, IC 95% 42.0–50.0 vs 58.1, IC 95% 56.0–60.2, respectively; p < 0.0001); patients with overweight and obesity presented significant higher plasma levels of TG than subjects with normal weight (257.3, IC 95% 231.6–283.0 and 290.9, IC 95% 245.5–336.4 vs 194.8, IC 95% 171.2–218.5, respectively; p < 0.0001), while no significant differences were observed between subjects affected by overweight and obesity (257.3, IC 95% 231.6–283.0 vs 290.9, IC 95% 245.5–336.4, respectively; p = 0.206). Non-HDL-C was significantly higher in patients with overweight than patients with normal weight (221.5, IC 95% 215.2–227.8 vs 210.1, IC 95% 204.3–216.0; p = 0.010), while no significant differences were observed between patients with overweight and with obesity (221.5, IC 95% 215.2–227.8 vs 219.6, IC 95% 208.4–230.7, respectively p = 0.766).

Fasting blood glucose was available in 431 patients and its level was significantly different among patients with overweight (92.0 mg/dL, IQR 87.0–101.0), with obesity (95.0 mg/dL, IQR 90.0–103.0) and with normal weight (89.0 mg/dL, IQR 82–94) with p < 0.0001. Considering the TyG index, we observed an analogous behavior, as its value was higher in patients with overweight (9.06, IQR 8.58–9.57) and obesity (9.18, IQR 8.67–9.68) that subjects with normal weight (8.57, IQR 8.16–9.03) with p = 0.036.

In a subgroup of 213 patients, we also collected waist circumference as it was available in their medical records. This measure was directly associated with SBP (r = 0.153, p = 0.025), while no statistically significant associations emerged in lipid profile. We found a non-statistically significant association with higher levels of waist circumference in patients with non-familial dyslipidemias (105.0, IQR 98.0–109.0, p = 0.071) as compared to FH (100.0, IQR 96.0–107.0), FCHL (100.5, IQR 95.0–106.0) and PH (99.0, IQR 97–106).