Comparison of lipoprotein and apolipoprotein levels in cord blood

Background: Hyperlipidemia is the primary risk factor for coronary artery disease and subsequently leading to morbidity and mortality in adulthood. It is a well-known fact that coronary artery disease can initiate in the fetal stage itself. The present study was planned to analyse cord blood lipoproteins and apolipoproteins levels and its association with gender and birth weight.Methods: This cross-sectional study was conducted in the Department of Biochemistry, in collaboration with Department of Gynecology and Obstetrics at SKIMS Medical College and Hospital, Bemina, Srinagar. A total 200 pregnant women who delivered by normal vaginal delivery and caesarean section were included in the study. 10 ml of umbilical cord blood was collected in a plain vial from the placental end within five minutes of delivery and serum lipoprotein and Apo-lipoprotein levels were measured.Results: Out of 200 newborns102 were males and 98 were females. Statistically significant difference was seen in parameters Apo A1, Apo B, Atherogenic index (Apo B/Apo A1) and LDL between the genders rest of the parameters were statistically. Also 32 newborns (16.0%) had 4000 grams birth weight. The mean lipoprotein and Apo-lipoprotein levels in these new born were compared between the groups. The mean serum levels of TC, TG, LDL and HDL were statistically significant (0.05) respectively.Conclusions: CVD being a leading cause of morbidity and mortality in the developing countries, early screening of the at risk babies i.e. low birth weight newborns using cord blood lipoproteins and apolipoproteins levels helps in primordial and primary prevention of diseases

Genetics of coronary heart disease with reference to ApoAI-CIII-AIV gene region.

Cardiovascular diseases are affected by multiple factors like genetic as well as environmental hence they reveal factorial nature. The evidences that genetic factors are susceptible for developing cardiovascular diseases come from twin studies and familial aggregation. Different ethnic populations reveal differences in the prevalence coronary artery disease (CAD) pointing towards the genetic susceptibility. With progression in molecular techniques different developments have been made to comprehend the disease physiology. Molecular markers have also assisted to recognize genes that may provide evidences to evaluate the role of genetic factors in causation of susceptibility towards CAD. Numerous studies suggest the contribution of specific "candidate genes", which correlate with various roles/pathways that are involved in the coronary heart disease. Different studies have revealed that there are large numbers of genes which are involved towards the predisposition of CAD. However, these reports are not consistent. One of the reasons could be weak contribution of genetic susceptibility of these genes. Genome wide associations show different chromosomal locations which dock, earlier unknown, genes which may attribute to CAD. In the present review different ApoAI-CIII-AIV gene clusters have been discussed

Risk factors, biochemical markers, and genetic polymorphisms in early coronary artery disease

OBJECTIVE: To assess the risk factors, lipid and apolipoprotein profile, hemostasis variables, and polymorphisms of the apolipoprotein AI-CIII gene in early coronary artery disease (CAD). METHODS: Case-control study with 112 patients in each group controlled by sex and age. After clinical evaluation and nutritional instruction, blood samples were collected for biochemical assays and genetic study. RESULTS: Familial history of early CAD (64 vs 39%), arterial hypertension (69 vs 36%), diabetes mellitus (25 vs 3%), and previous smoking (71 vs 46%) were more prevalent in the case group (p<0.001). Hypertension and diabetes were independent risk factors. Early CAD was characterized by higher serum levels of total cholesterol (235 ± 6 vs 209 ± 4 mg/dL), of LDL-c (154 ± 5 vs 135 ± 4 mg/dL), triglycerides (205 ± 12 vs 143 ± 9 mg/dL), and apolipoprotein B (129 ± 3 vs 105 ± 3 mg/dL), and lower serum levels of HDL-c (40 ± 1 vs 46 ± 1 mg/dL) and apolipoprotein AI (134 ± 2 vs 146 ± 2mg/dL) [p<0.01], in addition to an elevation in fibrinogen and D-dimer (p<0.02). The simultaneous presence of the rare alleles of the APO AI-CIII genes in early CAD are associated with hypertriglyceridemia (p=0.03). CONCLUSION: Of the classical risk factors, hypertension and diabetes mellitus were independently associated with early CAD. In addition to an unfavorable lipid profile, an increase in the thrombotic risk was identified in this population. An additive effect of the APO AI-CIII genes was observed in triglyceride levels.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo (UNIFESP) EPMUNIFESP, EPMSciEL

A study of omega-3 fatty acid therapy in patients with nephrotic syndrome

Patients with nephrotic range proteinuria have a higher risk of cardiovascular disease through qualitative and quantative changes in lipids and lipoproteins. The aim of this study was to examine the effect of omega-3 fatty acids derived from fish oil in this population. Treatment with omega-3 fatty acids in these patients was well tolerated and had a number of beneficial effects. They reduced small dense LDL concentration, remnant lipoproteins, VLDL and triglyceride level. Postprandial lipaemia was improved with an improvement in chylomicron clearance. However, we found that treatment increased LDL-C and although there was a redistribution to protective HDL2 rather than HDL3, HDL-C was not significantly increased. Furthermore, there was no improvement in endothelial function or inflammatory markers. Thus, we do not recommend treatment with omega-3 fatty acids alone for dyslipidaemia in this population of patients. The combination of omega-3 fatty acids with a statin merits further work

Metabolomics and coronary heart disease risk in UK Biobank

Background: Metabolomics is the comprehensive study of numerous metabolites from multiple molecular pathways using high-throughput methods such as nuclear magnetic resonance (NMR). Although the importance of some metabolites to coronary heart disease (CHD) risk is well established, such as low-density lipoprotein cholesterol (LDL-C), the relevance of many hundreds of other metabolites to CHD risk remains unclear. Objective: To assess the associations of NMR-derived plasma metabolites with incident CHD, and to evaluate the additional benefit of such metabolites to the prediction of 10-year cardiovascular risk. Methods: UK Biobank is a prospective study of 0.5 million adults aged 40-69 recruited in 2006-2010; in 2012-2013, a subset of the participants were resurveyed. NMR metabolites are currently available in a random subset of 118k participants. After excluding participants with prior cardiovascular disease and those taking statins, Cox regression models (adjusted for major potential confounders) were used to assess the association of each metabolite with CHD risk. Hazard ratios were corrected for regression dilution using the correlation of baseline and resurvey metabolic measures. The additional predictive value of metabolic profiling to an established risk score (QRISK) was evaluated with both Cox regression and machine-learning approaches. Results: After exclusions, 86,499 participants remained. There were 4,196 (4.9%) incident cases of CHD during a mean follow-up time of 11.5 years. CHD risk was positively associated with the concentrations of very-low-density (VLDL), intermediate-density (IDL), and low-density lipoproteins (LDL), and inversely associated with high-density lipoproteins (HDL). Hazard ratios (HRs) per standard deviation (SD) were 1.20 (95% CI 1.16-1.23), 1.15 (1.12-1.19), 1.17 (1.14-1.21) and 0.90 (0.87-0.91), respectively. There was little evidence that particle size of each of these lipoproteins was related to CHD risk. Given lipoprotein particle concentrations, lipid composition (including cholesterol) was not strongly related to CHD risk, except for triglyceride in LDL particles (HR 1.17 [1.11-1.23]). Independently of other fatty acids, CHD risk was positively associated with saturated fatty acids and monounsaturated fatty acids, inversely associated with omega-3 polyunsaturated fatty acids (PUFA), but there was no strong evidence of an association with omega-6 PUFA: HRs per SD higher fatty acid were 1.12 (1.07-1.17), 1.13 (1.08-1.18), 0.93 (0.90-0.97), and 1.02 (0.98-1.07), respectively. Independently of cholesterol and triglycerides, several non-lipid metabolites, including omega-3 fatty acids, glycine, histidine, albumin and glycoprotein acetyls, remained significantly associated with CHD risk. However, compared with QRISK, adding selected metabolites did not significantly improve measures of discrimination, reclassification or calibration. Conclusion: Of the lipoprotein characterization assessed, CHD risk was most strongly related to particle concentrations, suggesting that the major mechanism by which plasma lipids are related to CHD risk is through the concentration of lipoprotein particles that transport them. Independent of lipids, omega-3 PUFA and several low-molecular-weight metabolites remained significantly associated with CHD risk. However, there was no evidence that metabolic profiling improved cardiovascular risk prediction in UK primary care. Future research should further explore causality and mechanism pathways, and should include the assessment of the associations and predictive value in more diverse populations and wider-range of metabolites

Apolipoprotein Proteomics for Residual Lipid-Related Risk in Coronary Heart Disease

BACKGROUND: Recognition of the importance of conventional lipid measures and the advent of novel lipid-lowering medications have prompted the need for more comprehensive lipid panels to guide use of emerging treatments for the prevention of coronary heart disease (CHD). This report assessed the relevance of 13 apolipoproteins measured using a single mass-spectrometry assay for risk of CHD in the PROCARDIS case-control study of CHD (941 cases/975 controls). METHODS: The associations of apolipoproteins with CHD were assessed after adjustment for established risk factors and correction for statin use. Apolipoproteins were grouped into 4 lipid-related classes [lipoprotein(a), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides] and their associations with CHD were adjusted for established CHD risk factors and conventional lipids. Analyses of these apolipoproteins in a subset of the ASCOT trial (Anglo-Scandinavian Cardiac Outcomes Trial) were used to assess their within-person variability and to estimate a correction for statin use. The findings in the PROCARDIS study were compared with those for incident cardiovascular disease in the Bruneck prospective study (n=688), including new measurements of Apo(a). RESULTS: Triglyceride-carrying ApoC1, ApoC3, and ApoE (apolipoproteins) were most strongly associated with the risk of CHD (2- to 3-fold higher odds ratios for top versus bottom quintile) independent of conventional lipid measures. Likewise, ApoB was independently associated with a 2-fold higher odds ratios of CHD. Lipoprotein(a) was measured using peptides from the Apo(a)-kringle repeat and Apo(a)-constant regions, but neither of these associations differed from the association with conventionally measured lipoprotein(a). Among HDL-related apolipoproteins, ApoA4 and ApoM were inversely related to CHD, independent of conventional lipid measures. The disease associations with all apolipoproteins were directionally consistent in the PROCARDIS and Bruneck studies, with the exception of ApoM. CONCLUSIONS: Apolipoproteins were associated with CHD independent of conventional risk factors and lipids, suggesting apolipoproteins could help to identify patients with residual lipid-related risk and guide personalized approaches to CHD risk reduction