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

Characterization and intercomparison of aerosol absorption photometers: Result of two intercomparison workshops

Absorption photometers for real time application have been available since the 1980s, but the use of filter-based instruments to derive information on aerosol properties (absorption coefficient and black carbon, BC) is still a matter of debate. Several workshops have been conducted to investigate the performance of individual instruments over the intervening years. Two workshops with large sets of aerosol absorption photometers were conducted in 2005 and 2007. The data from these instruments were corrected using existing methods before further analysis. The inter-comparison shows a large variation between the responses to absorbing aerosol particles for different types of instruments. The unit to unit variability between instruments can be up to 30% for Particle Soot Absorption Photometers (PSAPs) and Aethalometers. Multi Angle Absorption Photometers (MAAPs) showed a variability of less than 5%. Reasons for the high variability were identified to be variations in sample flow and spot size. It was observed that different flow rates influence system performance with respect to response to absorption and instrumental noise. Measurements with non absorbing particles showed that the current corrections of a cross sensitivity to particle scattering are not sufficient. Remaining cross sensitivities were found to be a function of the total particle load on the filter. The large variation between the response to absorbing aerosol particles for different types of instruments indicates that current correction functions for absorption photometers are not adequate

Degenerative Veränderungen im alternden Innenohr, mit besonderer Berücksichtigung der vasculären Veränderungen, in Flächenpräparaten der menschlichen Cochlea dargestellt

Temporal bones from 150 patients, ranging in age from fetuses and newborn to 97 years, were studied by the technique of microdissection and the use of surface specimens stained with OSO 4 . Hair cell and nerve degeneration were seen in the extreme basal turn of the cochlea even in children. In the fetal cochlea vascularization is very dense, in the newborn and infant somewhat less so. A gradual involution of blood vessels occurs postnatally and continues with maturity and aging. Involution is seen especially in the membranous wall of the cochlea and in the system of spiral vessels of the basilar membrane and vestibular lip. During the first decade the radiating arterioles and the outer spiral vessel in the basal turn are reduced to their adult size. In presbycusis material we observed a marked loss of capillaries and of some of the radiating arterioles in the spiral ligament. Other arterioles had thickened walls. This devascularization was accompanied by atrophy and acellularity of the spiral ligament and atrophy of the stria. Atrophy of the spiral vessels was seen, especially in the lower half of the basal turn. Most of the cochlear blood vessels have clearly distinguishable perivascular spaces. Vessels which had become occluded and disappeared left behind them intervascular strands and/or avascular channels . Such channels were seen to connect the perivascular space of one capillary with that of another, representing the perivascular space of the vessel which had atrophied. The hair cell and nerve degeneration seen in presbycusis may be caused, at least in part, by microangiopathy of this type. Similar vascular changes have been observed in retinal vessels. It is possible that the gradual reduction of blood supply through the disappearance of capillaries occurs in many tissues of the body and plays an important role in the aging process. Mit Hilfe der Oberflächenpräparation wurden von uns 150 menschliche Labyrinthe aller Altersgruppen untersucht. Es wurde eine Haarzellen-und Nervendegeneration schon im Kindesalter beobachtet. Blutgefäße in der Schnecke haben perivasculdre Spalten; Gefäße atrophieren and werden zu „avascular channels”, leeren Spaltrdumen oder Striingen. Bei Presbyakusis fällt neben der Haarzell- and Nervendegeneration in der Basalwindung der Schnecke die Gefäßatrophie im Ligamentum spirale und der Membrana basilaris auf. Dazu kommt noch eine beträchtliche Atrophie des Ligamentum spirale und der Stria vascularis. Bemerkenswert ist, daß die Devascularisation schon im Kindesalter beginnt.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47255/1/405_2004_Article_BF00373313.pd

Characterization and intercomparison of aerosol absorption photometers: result of two intercomparison workshops

Absorption photometers for real time application have been available since the 1980s, but the use of filterbased instruments to derive information on aerosol properties (absorption coefficient and black carbon, BC) is still a matter of debate. Several workshops have been conducted to investigate the performance of individual instruments over the intervening years. Two workshops with large sets of aerosol absorption photometers were conducted in 2005 and 2007. The data from these instruments were corrected using existing methods before further analysis. The intercomparison shows a large variation between the responses to absorbing aerosol particles for different types of instruments. The unit to unit variability between instruments can be up to 30% for Particle Soot Absorption Photometers (PSAPs) and Aethalometers. Multi Angle Absorption Photometers (MAAPs) showed a variability of less than 5%. Reasons for the high variability were identified to be variations in sample flow and spot size. It was observed that different flow rates influence system performance with respect to response to absorption and instrumental noise. Measurements with non absorbing particles showed that the current corrections of a cross sensitivity to particle scattering are not sufficient. Remaining cross sensitivities were found to be a function of the total particle load on the filter. The large variation between the response to absorbing aerosol particles for different types of instruments indicates that current correction functions for absorption photometers are not adequate.

Characterization and intercomparison of aerosol absorption photometers: Result of two intercomparison workshops

Absorption photometers for real time application have been available since the 1980s, but the use of filter-based instruments to derive information on aerosol properties (absorption coefficient and black carbon, BC) is still a matter of debate. Several workshops have been conducted to investigate the performance of individual instruments over the intervening years. Two workshops with large sets of aerosol absorption photometers were conducted in 2005 and 2007. The data from these instruments were corrected using existing methods before further analysis. The inter-comparison shows a large variation between the responses to absorbing aerosol particles for different types of instruments. The unit to unit variability between instruments can be up to 30% for Particle Soot Absorption Photometers (PSAPs) and Aethalometers. Multi Angle Absorption Photometers (MAAPs) showed a variability of less than 5%. Reasons for the high variability were identified to be variations in sample flow and spot size. It was observed that different flow rates influence system performance with respect to response to absorption and instrumental noise. Measurements with non absorbing particles showed that the current corrections of a cross sensitivity to particle scattering are not sufficient. Remaining cross sensitivities were found to be a function of the total particle load on the filter. The large variation between the response to absorbing aerosol particles for different types of instruments indicates that current correction functions for absorption photometers are not adequate. © Author(s) 2011