Background The role of circulating FABP5 on metabolic alterations is under active evaluation. On the other hand, FABP5 SNPs (rs454550 and rs79370435) seem to modulate its effect. Objectives Our aim ...was to examine the role of circulating FABP5 levels and its main SNPs in atherogenic dyslipidemia (AD) assessed by 2D-Nuclear Magnetic Resonance (NMR) and related metabolic and inflammation markers. We hypothesized that circulating FABP5 may be a biomarker for metabolic risk. Methods We studied 459 subjects admitted to the metabolism unit because of lipid metabolism disturbances and/or associated disorders. After a 6-week lipid-lowering drug wash-out period, anamnesis and physical examination were performed. Carotid intime-media thickness (cIMT) was measured by ultrasound. FABP5, FABP4, lipids, metabolic proteins, and enzymes were determined by biochemical methods. The lipid profile was assessed by NMR. The rs454550 and rs79370435 FABP5 gene variants were also determined. Results The FABP5 plasma levels were positively correlated with adiposity, glucose metabolism, and lipolysis parameters and were associated with AD, as assessed by NMR. There was a significant positive correlation between hsCRP and FABP5. The presence of type 2 diabetes, obesity, metabolic syndrome, or AD was associated with higher FABP5 plasma levels ( P < .005). The FABP5 concentrations, but not those of FABP4, were higher in patients with carotid plaques. FABP5 was a main determinant of plaque presence according to logistic regression analysis. The rare rs454550 allele was hyper-represented in nonobese subjects ( P = .011). Conclusions FABP5 is a biomarker of adiposity-associated metabolic derangements that include AD thus underscoring the concomitant presence of inflammation. FABP5 is associated with increased subclinical atherosclerosis.
Aim: In heterozygous familial hypercholesterolaemic (FH) patients, study of the arterial wall and its function are of particular interest. Arterial stiffness has been shown to be associated with ...increased cardiovascular risk (CVR). In this study, we examined arterial stiffness in FH patients and its association with biochemical and vascular parameters. Methods: In this cross-sectional study, we included 125 FH patients (20-60 years old) and 59 gender- and age-matched healthy controls (CG). Clinical, anthropometry and biochemical data were obtained. Arterial stiffness determined based on the augmentation index (AIx) was assessed with peripheral artery tonometry. Carotid intima-media thickness (cIMT) and ankle-brachial index (ABI) were also assessed. Results: FH patients displayed a significant increase in AIx with respect to CG subjects (9.6±17.2 vs. 2.6±10.3%, P= 0.011). FH patients also had a thicker cIMT (0.758±0.280 vs. 0.635±0.160 mm, P< 0.001), while their ABIs were not different from CG subjects. AIx values were positively correlated with LDLc, non-HDLc, apolipoprotein B100, triglyceride and sE-selectin levels. Moreover, apolipoprotein B100-rich particles, along with systolic blood pressure and glucose levels, were the main determinants of AIx. In addition, we found that AIx (β= 0.224, P= 0.014) was an independent determinant of cIMT. Conclusions: FH patients have increased arterial stiffness, despite advancements in typical clinical management. AIx is clearly associated with apolipoprotein B100 concentrations, and it is a determinant of cIMT. AIx can be utilised as a vascular risk marker in FH patients.
Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and ...accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of HoFH.
Early diagnosis of HoFH and prompt initiation of diet and lipid-lowering therapy are critical. Genetic testing may provide a definitive diagnosis, but if unavailable, markedly elevated LDL-C levels together with cutaneous or tendon xanthomas before 10 years, or untreated elevated LDL-C levels consistent with heterozygous FH in both parents, are suggestive of HoFH. We recommend that patients with suspected HoFH are promptly referred to specialist centres for a comprehensive ACVD evaluation and clinical management. Lifestyle intervention and maximal statin therapy are the mainstays of treatment, ideally started in the first year of life or at an initial diagnosis, often with ezetimibe and other lipid-modifying therapy. As patients rarely achieve LDL-C targets, adjunctive lipoprotein apheresis is recommended where available, preferably started by age 5 and no later than 8 years. The number of therapeutic approaches has increased following approval of lomitapide and mipomersen for HoFH. Given the severity of ACVD, we recommend regular follow-up, including Doppler echocardiographic evaluation of the heart and aorta annually, stress testing and, if available, computed tomography coronary angiography every 5 years, or less if deemed necessary.
This EAS Consensus Panel highlights the need for early identification of HoFH patients, prompt referral to specialized centres, and early initiation of appropriate treatment. These recommendations offer guidance for a wide spectrum of clinicians who are often the first to identify patients with suspected HoFH.
Aims The aims of the study were, first, to critically evaluate lipoprotein(a) Lp(a) as a cardiovascular risk factor and, second, to advise on screening for elevated plasma Lp(a), on desirable levels, ...and on therapeutic strategies. Methods and results The robust and specific association between elevated Lp(a) levels and increased cardiovascular disease (CVD)/coronary heart disease (CHD) risk, together with recent genetic findings, indicates that elevated Lp(a), like elevated LDL-cholesterol, is causally related to premature CVD/CHD. The association is continuous without a threshold or dependence on LDL- or non-HDL-cholesterol levels. Mechanistically, elevated Lp(a) levels may either induce a prothrombotic/anti-fibrinolytic effect as apolipoprotein(a) resembles both plasminogen and plasmin but has no fibrinolytic activity, or may accelerate atherosclerosis because, like LDL, the Lp(a) particle is cholesterol-rich, or both. We advise that Lp(a) be measured once, using an isoform-insensitive assay, in subjects at intermediate or high CVD/CHD risk with premature CVD, familial hypercholesterolaemia, a family history of premature CVD and/or elevated Lp(a), recurrent CVD despite statin treatment, ≥3% 10-year risk of fatal CVD according to European guidelines, and/or ≥10% 10-year risk of fatal + non-fatal CHD according to US guidelines. As a secondary priority after LDL-cholesterol reduction, we recommend a desirable level for Lp(a) <80th percentile (less than ∼50 mg/dL). Treatment should primarily be niacin 1–3 g/day, as a meta-analysis of randomized, controlled intervention trials demonstrates reduced CVD by niacin treatment. In extreme cases, LDL-apheresis is efficacious in removing Lp(a). Conclusion We recommend screening for elevated Lp(a) in those at intermediate or high CVD/CHD risk, a desirable level <50 mg/dL as a function of global cardiovascular risk, and use of niacin for Lp(a) and CVD/CHD risk reduction.
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