**6. Adiponectin in members of families with familial combined hyperlipidemia**

Familial combined hyperlipidemia (FCH) is the most common genetic hyperlipidemia which affects 1.0% to 2.0% of the population. The lipids and lipoprotein levels are, however, only moderately elevated and do not fully explain the increased risk of cardiovascular disease. The aim of the study of Karásek et al. [43] was to evaluate plasma levels of adiponectin in asymptomatic, nonsmoking members of families with FCH. We also investigated the association between adiponectin and selected risk factors of atherosclerosis and markers of insulin resistance and chronic inflammation. Furthermore, we investigated the relationship between adiponectin and the intima-media thickness of the CCA (IMT), a recognized morphologic marker of early atherosclerosis.

#### **6.1. Subjects and methods**

The study was carried out with 82 members of 29 FCH families. A family with FCH was defined by a proband exhibiting plasma cholesterol and triglycerides concentrations above 90th percetile, adjusted for age and sex, based on data from the Czech population. At least one first-degree relative of the proband should have plasma cholesterol and/or triglycerides above 90th percentile, adjusted for age and sex, or level of apo B more than 1.25 g/l. Secondary hyperlipidemia was excluded by additional testing. Other exclusion criteria were a history of clinically manifest atherosclerosis, heart failure, cerebrovascular ischemic disease, peripheral vascular disease, smoking, hypolipidemic therapy in the previous 8 weeks, hormone therapy with estrogens and acute infection or trauma. Members of FCH were divided into 2 groups: HL (hyperlipidemic members of FCH families, i.e. probands and their hyperlipidemic first-degree relatives) and NL (normolipidemic first-degree relatives). The control groups, C-HL and C-NL, were sex and age matched to groups. Control groups consisted of healthy individuals with a negative family history of hyperlipidemia and early manifestation of atherosclerosis. Nobody was treated for hypertension.

Laboratory parameters were analyzed by routine methods described above. Ultrasound scanning was performed with a 10 MHz linear array transducer (Hewlett-Packard, Image Point, M2410A). All measurements were performed with the subjects in a supine position. Three video records were made of common carotid artery (CCA). IMT measurements were processed off-line using software Image-Pro Plus (v. 4.0, Media-Cybernetics, Silver Spring). The average of the IMT of 3 frozen images of both sides was chosen as the outcome variable. Subjects with an atherosclerotic plaque in the evaluated region were not included in the study. The measurement of IMT was made without knowledge of laboratory results.

#### **6.2. Results**

694 Lipoproteins – Role in Health and Diseases

syndrome should be continue to observe.

recognized morphologic marker of early atherosclerosis.

**5.4. Conclusions** 

**hyperlipidemia** 

**6.1. Subjects and methods** 

The highest levels of ADP were observed in DLP1 (no significance). Suprisingly, there was seen no negative association between adiponectin levels and DLP2 (DLP4). FGF 21 and A-FABP were significantly increased in the groups with the most important atherogenic potential (DLP2, DLP4). These two parameters correlated with higher levels of triglycerides,

No association was found between ADP levels and other adipokines in DLP groups in our study. There was the correlation between FGF 21 and A-FABP in groups with TGL > 1.5 mmol/l. Increased levels of both parameters were associated with increased glucose, BMI and decreased HDL cholesterol levels (in accordance with lit.[40]). The increase of FGF 21 concentrations are probably due to the compensatory response to higher A-FABP that is considered the predictor of metabolic syndrome. In individuals with MS, the determination of A-FABP could be considered as a parameter with the independent metabolic effects [42]. The clinical potential especially of A-FABP in diagnostics and prediction of metabolic

Familial combined hyperlipidemia (FCH) is the most common genetic hyperlipidemia which affects 1.0% to 2.0% of the population. The lipids and lipoprotein levels are, however, only moderately elevated and do not fully explain the increased risk of cardiovascular disease. The aim of the study of Karásek et al. [43] was to evaluate plasma levels of adiponectin in asymptomatic, nonsmoking members of families with FCH. We also investigated the association between adiponectin and selected risk factors of atherosclerosis and markers of insulin resistance and chronic inflammation. Furthermore, we investigated the relationship between adiponectin and the intima-media thickness of the CCA (IMT), a

The study was carried out with 82 members of 29 FCH families. A family with FCH was defined by a proband exhibiting plasma cholesterol and triglycerides concentrations above 90th percetile, adjusted for age and sex, based on data from the Czech population. At least one first-degree relative of the proband should have plasma cholesterol and/or triglycerides above 90th percentile, adjusted for age and sex, or level of apo B more than 1.25 g/l. Secondary hyperlipidemia was excluded by additional testing. Other exclusion criteria were a history of clinically manifest atherosclerosis, heart failure, cerebrovascular ischemic disease, peripheral vascular disease, smoking, hypolipidemic therapy in the previous 8 weeks, hormone therapy with estrogens and acute infection or trauma. Members of FCH were divided into 2 groups: HL (hyperlipidemic members of FCH families, i.e. probands

fasting glucose, BMI and lower HDL cholesterol, both in DLP2 and DLP4.

**6. Adiponectin in members of families with familial combined** 

In comparison to sex and age matched controls, HL subjects had significantly higher diastolic blood pressure (DBP), BMI, insulin resistance and elevated levels of C-peptide and proinsulin. They had higher IMT, hsCRP and ICAM 1 as well. By definition, the FCH subjects showed higher plasma cholesterol and triglycerides concentrations compared with controls and normolipidemic relatives. They had a more atherogenic lipid and lipoprotein profile as reflected by increased LDL cholesterol and apo B concentrations. Normolipidemic relatives had significantly higher DBP, TGL and proinsulin concentrations compared with their sex and age matched controls. There was no difference in other measured anthropometric and biochemical parameters.

Compared with healthy controls, HL subjects had lower levels of adiponectin (13.02 ± 4.58 mg/l vs. 16.19 ± 5.39 mg/l, p < 0.05). In the NL relatives, there was no significant differences in adiponectin (15.77 ± 2.95 mg/l vs. 16.53 ± 4.26 mg/l). In all FCH families, a significant negative correlation was found between adiponectin and TGL (r = - 0.35, p < 0.01), proinsulin (r = - 0.26, p < 0.05), hsCRP (r = - 0.24, p < 0.05), BMI (r = - 0.27, p < 0.05) and waist circumference (r = -0.32, p < 0.01). Levels of adiponectin did not correlate with IMT, in members of FCH families or in controls. By using regression model in HL subjects, levels of adiponectin were predicted by apo B (p < 0.05) and hsCRP (p < 0.05). (More detailed results are given in lit. [43].)

#### **6.3. Discussion and conclusions**

This study reported decreased adiponectin levels in asmyptomatic hyperlipidemic members of FCH families. There was no difference in serum adiponectin levels between their firstdegree normolipidemic relatives and healthy controls. A negative correlation between adiponectin and markers of insulin resistance, chronic inflammation and visceral obesity was found in FCH families. The results were consistent with previous findings and support an insulin-sensitizing effect of adiponectin. In hyperlipidemic individuals, the levels of plasma adiponectin were predicted by apolipoprotein B and high sensitive CRP, independent of insuline resistance and visceral obesity. Authors conclude low adiponectin levels are associated with proinflammatory status and insulin resistance, and could partially explain the increased risk of coronary heart disease, even if the lipids and lipoprotein levels are only moderately elevated.

The study did not confirm any correlation between adiponectin levels and IMT, a marker of subclinical atherosclerosis, in FCH subjects. Publications regarding the relationship between these parameters are not entirely consistent. Similar results were observed in other work published by Karásek et al [44] where IMT proved to correlate with age, lipid parameters, markers of insulin resistance and that of visceral obesity and blood pressure. These parameters seem to be risk factors instead of adiponectin. The lack of correlation between adiponectin and IMT does not argue for adiponectin as an independent predictor for next cardiovascular events in clinically asymptomatic, dyslipidemic individuals.
