Computationally estimated apolipoproteins B and A1 in predicting cardiovascular risk
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku and Turku University Central Hospital, Turku, Finland. Electronic address: . Atherosclerosis
(Impact Factor: 3.99).
11/2012; 226(1). DOI: 10.1016/j.atherosclerosis.2012.10.049
Apolipoproteins B (apoB) and A1 (apoA1) may be better markers of atherosclerosis than serum lipids. We used computational methods to estimate apoB and apoA1 from serum total cholesterol, HDL-cholesterol and triglycerides and tested their clinical value in comparison to measured apoB and apoA1 values.
ApoB and apoA1 were measured with standard methods and estimated based on neural network regression models in 2166 young adult with data on carotid artery intima-media thickness (cIMT).
Correlations between estimated and measured apoB and apoA1 were r = 0.98 and r = 0.95, respectively. ApoB/apoA1-ratio (both measured and estimated) associated with cIMT in multivariable models, and predicted cIMT at all levels of LDL-cholesterol concentration. Strong correlations between the estimated apolipoproteins and those measured from fasting samples were replicated in over 15,000 Caucasian subjects (r = 0.93-0.96 for apoB and r = 0.91-0.92 for apoA1). Correlations with cIMT were replicated in over 2000 individuals. Estimated apoB/apoA1-ratio calculated from non-fasting lipids in over 20,000 individuals in the INTERHEART study was better than any of the cholesterol measures for estimation of the myocardial risk.
Serum cholesterol, HDL-cholesterol and triglycerides can be used to compute clinically useful estimates of apoB and apoA1. Using this methodology, estimates of apolipoproteins could be routinely added to laboratory reports to complement lipoprotein lipids in risk assessment.
Available from: Jaakko Tuomilehto
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Low serum 25-hydroxyvitamin D (25OHD) level has been associated with an increased risk of several chronic diseases. Our aim was to determine lifestyle and clinical factors that are associated with 25OHD level and to investigate connection of 25OHD level with metabolic and cardiovascular disease markers.
In total, 2868 Finnish men and women aged 45–74 years participated in FIN-D2D population-based health survey in 2007. Participants that had a serum sample available (98.4%; n = 2822) were included in this study. 25OHD was measured with chemiluminescent microparticle immunoassay method.
The mean 25OHD level was 58.2 nmol/l in men (n = 1348) and 57.1 nmol/l in women (n = 1474). Mean 25OHD level was lower in the younger age groups than in the older ones (p<0.0001 both in men and women). This study confirmed that low physical activity (p<0.0001 both in men and women), smoking (p = 0.0002 in men and p = 0.03 in women) and high BMI (p<0.0001 in women) are factors that independently associate with low 25OHD level. Of the metabolic and cardiovascular disease markers high triglyceride concentration (p = 0.02 in men and p = 0.001 in women) and high apolipoprotein B/apolipoprotein A1 ratio (p = 0.04 in men and p = 0.03 in women) were independently associated with low 25OHD level.
Higher age did not predict lower 25OHD level in this study population of aged 45–74 years which may derive from a healthy life-style of “active pensioners”. Low physical activity and smoking came up as independent lifestyle factors associated with low 25OHD level. Defining the molecular mechanisms behind the associations of 25OHD with low physical activity and smoking are important objective in future studies. The association of 25OHD with BMI, high triglyceride concentration and apolipoprotein B/apolipoprotein A1 ratio may be related to the role of vitamin D in inflammation, but more detailed studies are needed.
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ABSTRACT: Epidemiological studies have shown an inverse association between high-density lipoprotein cholesterol (HDL-C) levels and risk of ischemic heart disease. In addition, a low level of HDL-C has been shown to be a risk factor for other diseases not related to atherosclerosis. However, recent studies have not supported a causal effect of HDL-C in the development of atherosclerosis. Furthermore, new drugs markedly elevating HDL-C levels have been disappointing with respect to clinical endpoints. Earlier, most studies have focused almost exclusively on the total HDL-C without regard to the chemical composition or multiple subclasses of HDL particles. Recently, there have been efforts to dissect the HDL fraction into as many well-defined subfractions and individual molecules of HDL particles as possible. On the other hand, the focus is shifting from the structure and composition to the function of HDL particles. Biomarkers and mechanisms that could potentially explain the beneficial characteristics of HDL particles unrelated to their cholesterol content have been sought with sophisticated methods such as proteomics, lipidomics, metabonomics, and function studies including efflux capacity. These new approaches have been used in order to resolve the complex effects of diseases, conditions, environmental factors, and genes in relation to the protective role of HDL but high-throughput methods are still needed for large-scale epidemiological studies.
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