Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium.

BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research

Architectures for block Toeplitz systems

In this paper efficient VLSI architectures of highly concurrent algorithms for the solution of block linear systems with Toeplitz or near-to-Toeplitz entries are presented. The main features of the proposed scheme are the use of scalar only operations, multiplications/divisions and additions, and the local communication which enables the development of wavefront array architecture. Both the mean squared error and the total squared error formulations are described and a variety of implementations are given

A survey of the state of the art and focused research in range systems, task 2

Contract generated publications are compiled which describe the research activities for the reporting period. Study topics include: equivalent configurations of systolic arrays; least squares estimation algorithms with systolic array architectures; modeling and equilization of nonlinear bandlimited satellite channels; and least squares estimation and Kalman filtering by systolic arrays

A survey of the state-of-the-art and focused research in range systems

In this one-year renewal of NASA Contract No. 2-304, basic research, development, and implementation in the areas of modern estimation algorithms and digital communication systems have been performed. In the first area, basic study on the conversion of general classes of practical signal processing algorithms into systolic array algorithms is considered, producing four publications. Also studied were the finite word length effects and convergence rates of lattice algorithms, producing two publications. In the second area of study, the use of efficient importance sampling simulation technique for the evaluation of digital communication system performances were studied, producing two publications

Large-Scale MIMO Detection for 3GPP LTE: Algorithms and FPGA Implementations

Large-scale (or massive) multiple-input multiple-output (MIMO) is expected to be one of the key technologies in next-generation multi-user cellular systems, based on the upcoming 3GPP LTE Release 12 standard, for example. In this work, we propose - to the best of our knowledge - the first VLSI design enabling high-throughput data detection in single-carrier frequency-division multiple access (SC-FDMA)-based large-scale MIMO systems. We propose a new approximate matrix inversion algorithm relying on a Neumann series expansion, which substantially reduces the complexity of linear data detection. We analyze the associated error, and we compare its performance and complexity to those of an exact linear detector. We present corresponding VLSI architectures, which perform exact and approximate soft-output detection for large-scale MIMO systems with various antenna/user configurations. Reference implementation results for a Xilinx Virtex-7 XC7VX980T FPGA show that our designs are able to achieve more than 600 Mb/s for a 128 antenna, 8 user 3GPP LTE-based large-scale MIMO system. We finally provide a performance/complexity trade-off comparison using the presented FPGA designs, which reveals that the detector circuit of choice is determined by the ratio between BS antennas and users, as well as the desired error-rate performance.Comment: To appear in the IEEE Journal of Selected Topics in Signal Processin