Fifty-three year follow-up of coronary heart disease versus HDL2 and other lipoproteins in Gofman's Livermore Cohort
Bibliographic record
Abstract
To assess the relationships of lipoprotein mass concentrations to all-cause and coronary heart disease (CHD) mortality, we analyzed the prospective 53-year follow-up of 1,905 men measured for lipoprotein mass concentrations by analytic ultracentrifugation between 1954 and 1957. Cause of death was determined from medical records and death certificates before 1979 and from National Death Index death diagnoses thereafter. Of the 1,329 men (69.8%) who died through 2008, CHD was listed as a contributing cause of death for 409 men, including 113 deaths from premature CHD (age ≤ 65 years). When adjusted for age, the risk associated with the lowest HDL2 quartile increased 22% for all-cause (P= 0.001), 63% for total CHD (P < 10−5), and 117% for premature CHD mortality (P= 0.0001). When adjusted for standard risk factors (age, total cholesterol, blood pressure, BMI, smoking) and the lowest HDL3 quartile, the corresponding risk increases were 14% (P= 0.05), 38% (P= 0.004), and 62% (P= 0.02), respectively. Men with HDL3 ≤ 25th percentile had 28% greater total CHD risk (P= 0.03) and 71% greater premature CHD risk (P= 0.01). Higher LDL-mass concentrations increased total CHD risk by 3.8% (P < 10−9) and premature CHD risk by 6.1% (P < 10−7) per 10 mg/dl increase in concentration. Thus, low HDL2 is associated with increased CHD risk. To assess the relationships of lipoprotein mass concentrations to all-cause and coronary heart disease (CHD) mortality, we analyzed the prospective 53-year follow-up of 1,905 men measured for lipoprotein mass concentrations by analytic ultracentrifugation between 1954 and 1957. Cause of death was determined from medical records and death certificates before 1979 and from National Death Index death diagnoses thereafter. Of the 1,329 men (69.8%) who died through 2008, CHD was listed as a contributing cause of death for 409 men, including 113 deaths from premature CHD (age ≤ 65 years). When adjusted for age, the risk associated with the lowest HDL2 quartile increased 22% for all-cause (P= 0.001), 63% for total CHD (P < 10−5), and 117% for premature CHD mortality (P= 0.0001). When adjusted for standard risk factors (age, total cholesterol, blood pressure, BMI, smoking) and the lowest HDL3 quartile, the corresponding risk increases were 14% (P= 0.05), 38% (P= 0.004), and 62% (P= 0.02), respectively. Men with HDL3 ≤ 25th percentile had 28% greater total CHD risk (P= 0.03) and 71% greater premature CHD risk (P= 0.01). Higher LDL-mass concentrations increased total CHD risk by 3.8% (P < 10−9) and premature CHD risk by 6.1% (P < 10−7) per 10 mg/dl increase in concentration. Thus, low HDL2 is associated with increased CHD risk. In 1954, John Gofman and colleagues reported that analytic ultracentrifuge measurements of high-density lipoproteins (HDL) in blood revealed two particle subclasses, HDL2 and HDL3, and that the concentrations of the more buoyant particles (HDL2) were 50% higher in women than men (1Lindgren F.T. Elliott H.A. Gofman J.W. The ultracentrifugal characterization and isolation of human blood lipids and lipoproteins, with applications to the study of atherosclerosis.J. Phys. Colloid Chem. 1951; 55: 80-93Crossref PubMed Scopus (80) Google Scholar, 2De Lalla O.F. Gofman J.W. Ultracentrifugal analysis of serum lipoproteins.Methods Biochem. Anal. 1954; 1: 459-478Crossref PubMed Google Scholar). In 1966, they reported that 38 men who developed coronary heart disease (CHD) had HDL mass concentrations that were 32% lower for HDL2 and 8% lower for HDL3 (the less buoyant particles) compared with those who did not develop CHD (3Gofman J.W. Young W. Tandy R. Ischemic heart disease, atherosclerosis, and longevity.Circulation. 1966; 34: 679-697Crossref PubMed Scopus (423) Google Scholar). Gofman's initial observation gave rise to studies by others on the potential clinical utility of HDL2 and HDL3 measurements. Rather than employing Gofman's original methodology, they measured HDL2- and HDL3-cholesterol by precipitation and HDL size classes by nuclear magnetic resonance (NMR) or, more rarely, ultracentrifugation. Many studies showed that high HDL2 was associated with lower CHD risk (4Fujimoto W.Y. Bergstrom R.W. Boyko E.J. Chen K.W. Leonetti D.L. Newell-Morris L. Shofer J.B. Wahl P.W. Visceral adiposity and incident coronary heart disease in Japanese-American men. The 10-year follow-up results of the Seattle Japanese-American Community Diabetes Study.Diabetes Care. 1999; 22: 1808-1812Crossref PubMed Scopus (260) Google Scholar, 5Laakso M. Lehto S. Penttilä I. Pyörälä K. Lipids and lipoproteins predicting coronary heart disease mortality and morbidity in patients with non-insulin-dependent diabetes.Circulation. 1993; 88: 1421-1430Crossref PubMed Scopus (308) Google Scholar, 6Lamarche B. Moorjani S. Cantin B. Dagenais G.R. Lupien P.J. Després J.P. Associations of HDL2 and HDL3 subfractions with ischemic heart disease in men. Prospective results from the Québec Cardiovascular Study.Arterioscler. Thromb. Vasc. Biol. 1997; 17: 1098-1105Crossref PubMed Scopus (161) Google Scholar, 7Salonen J.T. Salonen R. Seppänen K. Rauramaa R. Tuomilehto J. HDL, HDL2, and HDL3 subfractions, and the risk of acute myocardial infarction. A prospective population study in eastern Finnish men.Circulation. 1991; 84: 129-139Crossref PubMed Scopus (330) Google Scholar, 8Sharrett A.R. Ballantyne C.M. Coady S.A. Heiss G. Sorlie P.D. Catellier D. Patsch W. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: the Atherosclerosis Risk in Communities (ARIC) Study.Circulation. 2001; 104: 1108-1113Crossref PubMed Scopus (781) Google Scholar, 9Stampfer M.J. Sacks F.M. Salvini S. Willett W.C. Hennekens C.H. A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction.N. Engl. J. Med. 1991; 325: 373-381Crossref PubMed Scopus (1032) Google Scholar, 10Mora S. Otvos J.D. Rifai N. Rosenson R.S. Buring J.E. Ridker P.M. Lipoprotein particle profiles by nuclear magnetic resonance compared with standard lipids and apolipoproteins in predicting incident cardiovascular disease in women.Circulation. 2009; 119: 931-939Crossref PubMed Scopus (374) Google Scholar); however, the independent effects of HDL2 and HDL3 on CHD risk remained inconclusive (5Laakso M. Lehto S. Penttilä I. Pyörälä K. Lipids and lipoproteins predicting coronary heart disease mortality and morbidity in patients with non-insulin-dependent diabetes.Circulation. 1993; 88: 1421-1430Crossref PubMed Scopus (308) Google Scholar, 7Salonen J.T. Salonen R. Seppänen K. Rauramaa R. Tuomilehto J. HDL, HDL2, and HDL3 subfractions, and the risk of acute myocardial infarction. A prospective population study in eastern Finnish men.Circulation. 1991; 84: 129-139Crossref PubMed Scopus (330) Google Scholar, 8Sharrett A.R. Ballantyne C.M. Coady S.A. Heiss G. Sorlie P.D. Catellier D. Patsch W. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: the Atherosclerosis Risk in Communities (ARIC) Study.Circulation. 2001; 104: 1108-1113Crossref PubMed Scopus (781) Google Scholar, 9Stampfer M.J. Sacks F.M. Salvini S. Willett W.C. Hennekens C.H. A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction.N. Engl. J. Med. 1991; 325: 373-381Crossref PubMed Scopus (1032) Google Scholar, 10Mora S. Otvos J.D. Rifai N. Rosenson R.S. Buring J.E. Ridker P.M. Lipoprotein particle profiles by nuclear magnetic resonance compared with standard lipids and apolipoproteins in predicting incident cardiovascular disease in women.Circulation. 2009; 119: 931-939Crossref PubMed Scopus (374) Google Scholar). Currently, the National Cholesterol Education Program Adult Treatment Panel (ATP-III) guidelines (11Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in AdultsExecutive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).J AMA. 2001; 285: 2486-2497Crossref PubMed Scopus (24245) Google Scholar) state that “although small studies suggest greater predictive power of one or another HDL component, their superiority over HDL-cholesterol has not been demonstrated in large, prospective studies. Consequently, ATP III does not recommend the routine measurement of HDL subspecies in CHD risk assessment.” However, the clinical utility of HDL subclasses may be underappreciated in part due to the limitations of these alternative methods to adequately characterize HDL heterogeneity (12Williams P.T. Krauss R.M. Vranizan K.M. Stefanick M.L. Wood P.D. Lindgren F.T. Associations of lipoproteins and apolipoproteins with gradient gel electrophoresis estimates of high density lipoprotein subfractions in men and women.Arterioscler. Thromb. 1992; 12: 332-340Crossref PubMed Google Scholar, 13Franceschini G. Tosi C. Moreno Y. Sirtori C.R. Effects of storage on the distribution of high density lipoprotein subfractions in human sera.J. Lipid Res. 1985; 26: 1368-1373Abstract Full Text PDF PubMed Google Scholar, 14Daerr W.H. Windler E.E. Rohwer H.D. Greten H. Limitations of a new double-precipitation method for the determination of high density lipoprotein subfractions 2 and 3.Atherosclerosis. 1983; 49: 211-213Abstract Full Text PDF PubMed Scopus (6) Google Scholar, 15Johansson J. Nilsson-Ehle P. Carlson L.A. Hamsten A. The association of lipoprotein and hepatic lipase activities with high density lipoprotein subclass levels in men with myocardial infarction at a young age.Atherosclerosis. 1991; 86: 111-122Abstract Full Text PDF PubMed Scopus (33) Google Scholar, 16Otvos J.D. Jeyarajah E.J. Bennett D.W. Krauss R.M. Development of a proton nuclear magnetic resonance spectroscopic method for determining plasma lipoprotein concentrations and subspecies distributions from a single, rapid measurement.Clin. Chem. 1992; 38: 1632-1638Crossref PubMed Scopus (375) Google Scholar). Between 1954 and 1956, John Gofman created a cohort of 1,905 men in whom lipoproteins were measured by analytic ultracentrifugation (3Gofman J.W. Young W. Tandy R. Ischemic heart disease, atherosclerosis, and longevity.Circulation. 1966; 34: 679-697Crossref PubMed Scopus (423) Google Scholar). Our rediscovery of Gofman's original data enabled us to assess the relationships of lipoprotein mass concentrations to CHD during 29-year follow-up (17Williams P.T. Feldman D.E. Prospective study of coronary heart disease vs. HDL2, HDL3, and other lipoproteins in Gofman's Livermore Cohort.Atherosclerosis. 2011; 214: 196-202Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar). Those analyses showed that i) the lowest quartile of HDL2-mass increased the men's risks of fatal plus nonfatal CHD by 38% and their risks of premature CHD (age ≤ 65 years) by 61% when adjusted for traditional risk factors, ii) the HDL2-CHD risk relationship remained significant when adjusted for HDL3, and iii) the risk reduction per mg/dl of HDL-mass was significantly greater for HDL2 than HDL3 (17Williams P.T. Feldman D.E. Prospective study of coronary heart disease vs. HDL2, HDL3, and other lipoproteins in Gofman's Livermore Cohort.Atherosclerosis. 2011; 214: 196-202Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar). The current report extends the mortality surveillance of Gofman's cohort from 29 to 53 of the relationships between lipoproteins and disease and HDL2 CHD risk and mortality independent of total HDL The cohort of of the Livermore Livermore National who to blood between 1954 and and to be (3Gofman J.W. Young W. Tandy R. Ischemic heart disease, atherosclerosis, and longevity.Circulation. 1966; 34: 679-697Crossref PubMed Scopus (423) Google Scholar). The men to the 1,905 of Gofman's original report who were of ischemic heart disease at The for the study to the by the the predictive of serum lipoprotein and total cholesterol on clinical of atherosclerosis, in Gofman J.W. M. L.A. of serum lipoprotein and cholesterol measurements as of clinical of report of a study of lipoproteins and Google Scholar). potential were on the of more than of or of or of with or of heart heart or or blood pressure, and blood were during the medical was determined by total cholesterol was by a of the method method for determination of total serum J. 26: PubMed Scopus (6) Google Scholar). and high-density lipoprotein concentrations were by analytic ultracentrifugation (3Gofman J.W. Young W. Tandy R. Ischemic heart disease, atherosclerosis, and longevity.Circulation. 1966; 34: 679-697Crossref PubMed Scopus (423) Google Scholar). The follow-up of the cohort was by the for the of of at surveillance follow-up of the cohort through with of and death certificates (17Williams P.T. Feldman D.E. Prospective study of coronary heart disease vs. HDL2, HDL3, and other lipoproteins in Gofman's Livermore Cohort.Atherosclerosis. 2011; 214: 196-202Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar). between and were through the National Death Index for Death Index of and and for the cause of death and contributing listed in the The current analyses CHD as through from the of for deaths between 1979 and and as through from the of analyses and analyses were with their were from the the of was by the that they by The for a a HDL the of HDL mg/dl concentrations and for the lowest HDL quartile in the with a of the and of the per mg/dl as of a the of the 1,905 men in the were were between and were between and and less than of one were 65 or were of as measured by mass < were < and were of the men were blood or blood and had serum total cholesterol on the distribution of the cholesterol and lipoprotein mass and for all-cause and CHD mortality risk factors during 53-year blood pressure, BMI, and mg/dl lipoprotein per 10 in blood pressure, in BMI, or 10 mg/dl in lipoprotein CHD mortality CHD mortality (age ≤ 65 < < < < < < < blood in a new blood Of the 1,329 men (69.8%) who died through 2008, CHD was listed as a contributing cause in the death of 409 men, including 113 deaths from premature CHD (age ≤ the for all-cause and CHD greater BMI, and blood increased the men's risk for all-cause and CHD mortality during the 53 of serum total cholesterol concentrations increased their risk for not for The effects of on all-cause mortality to be to the effects of blood and to significant increases in the risks for deaths increased with to blood per 10 to and blood per 10 to 2 that per blood pressure, and total cholesterol increased the risks for total and premature CHD when in for reported total and premature CHD traditional risk factors and lipoprotein mass CHD (age ≤ 65 subfractions and subfractions and 10 < < < 10 cholesterol 10 10 < 10 10 10 from the adjusted for the other in to were 409 total in 1,905 men, and 113 premature CHD in men men were for 65 or at blood in a new The from the adjusted for the other in to were 409 total in 1,905 men, and 113 premature CHD in men men were for 65 or at blood Higher serum HDL2 concentrations were significantly to total premature and all-cause mortality In the lowest HDL2 quartile had a 63% increased CHD risk to through (P < not increased risk for fatal CHD was by for total HDL HDL2 HDL3, to or to 0.0001). The lowest HDL2 quartile had greater on the risk for premature fatal CHD to when adjusted for total HDL to or HDL3 to in to The lowest association with all-cause mortality was to when adjusted for total HDL to or HDL3 to in to that the of the risk reduction between the and HDL2 the effects of HDL3 and total on the HDL2-CHD 2 that the total CHD risk associated with the lowest HDL2 quartile remained significant when adjusted for standard risk factors and the lowest HDL3 quartile (P= and when the risk reduction was greater for premature than total CHD analyses showed that when the of HDL2-mass per 10 and the lowest quartile of HDL2 were in the the lowest HDL2 quartile was significantly to all-cause (P= 0.05), total CHD (P= and premature CHD deaths (P= 0.02), the effects were not (P= and analyses a in CHD risk with concentrations of HDL2 mass and suggest a in risk associated with low the analyses the showed that the lowest quartile of HDL2 increased the for total CHD deaths by (P < and premature CHD deaths by (P= 0.0001). increased for total and premature CHD remained significant when adjusted for total HDL (P= and HDL3 (P= and or standard risk factors (P= and When the of HDL2 mass and the lowest quartile of HDL2 were in the the of the lowest HDL2 quartile for total CHD (P= and premature CHD deaths (P= and the of the (P= and analyses to the lowest HDL2 quartile for the for all-cause mortality (P= was by for standard risk factors (P= When adjusted for and for standard risk factors, serum HDL3 concentrations significantly the risk for total CHD and premature CHD deaths not the risks for all-cause mortality The reduction in CHD risk per 10 mg/dl of concentrations when adjusted for HDL2-mass concentrations and standard risk factors (P= analyses the of fatal CHD for concentrations of reduction per 10 and the increased for the lowest HDL3 quartile 0.03) and their when adjusted for standard risk factors (P= and including HDL2 (P= and Higher LDL-mass concentrations significantly increased the risk for total and premature CHD mortality when adjusted for small significant on total mortality is to CHD mortality, as had significant on mortality (P= not 2 that CHD risk increased with LDL-mass and that for total cholesterol concentrations had on the risk for LDL-mass concentrations the significant of total cholesterol on CHD risk in analysis that adjusted for < to not or when adjusted for standard risk factors, and Higher concentrations of small and increased CHD risk when adjusted for and were not significant when adjusted for and standard risk analyses the increased for CHD mortality with mass concentrations of (P < (P < small (P < and (P= the of when with and standard risk factors (P= and the of the of total cholesterol when adjusted for LDL-mass concentrations to CHD was as the cause of death in of the 409 men who had CHD listed as a contributing cause the of the National Death Index the analyses to CHD as cause results with the with the lowest HDL2 quartile was significantly associated with total CHD risk when adjusted for to and when adjusted for standard risk factors plus the lowest HDL3 quartile to was significant for a risk increase for the lowest HDL2 quartile a in CHD risk per mg/dl in HDL2 (P= 0.01). CHD risk increased significantly per 10 mg/dl increase in LDL-mass concentrations when adjusted for to < and when adjusted for the standard risk factors to CHD risk was not significantly to concentrations or the lowest HDL3 quartile The 53-year follow-up of Gofman's Livermore is the study of CHD to lipoproteins and HDL The results the of HDL2 as a CHD risk independent of traditional CHD risk factors (age, blood pressure, BMI, total HDL3, and total HDL they that the of the risk the lowest HDL2 results significant they from on other HDL2- and HDL3-cholesterol to the of one over another or of their over total HDL-cholesterol (11Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in AdultsExecutive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).J AMA. 2001; 285: 2486-2497Crossref PubMed Scopus (24245) Google Scholar). they report that the relationship of HDL-cholesterol to CHD risk is (11Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in AdultsExecutive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).J AMA. 2001; 285: 2486-2497Crossref PubMed Scopus (24245) Google in to the HDL2-mass concentrations in is between the risk estimates for fatal and nonfatal CHD during the 29-year follow-up of cohort and the risk estimates for the more of fatal CHD during 53 of The 29-year follow-up CHD deaths the total fatal and nonfatal CHD is less than of the 409 fatal CHD analyzed in the current The current guidelines not routine clinical measurement of HDL subfractions (11Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in AdultsExecutive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).J AMA. 2001; 285: 2486-2497Crossref PubMed Scopus (24245) Google Scholar). may been premature to the of HDL subclasses from studies on other In the to the independent effects of HDL2 or HDL3 may to their on HDL2- and analyses of the data from men who in studies at showed between HDL-cholesterol and total HDL-mass P.D. Stefanick M.L. P.T. The effects on plasma lipoproteins of a with or in men and Engl. J. Med. 1991; 325: PubMed Scopus Google Scholar, P.D. Stefanick M.L. B. P.T. Vranizan K.M. in plasma lipids and lipoproteins in men during through as compared with Engl. J. Med. PubMed Scopus Google Scholar). HDL-cholesterol and by precipitation R. J. J. of high density lipoprotein subclasses by and Chem. PubMed Scopus Google with HDL2-mass concentrations and in these however, the higher In of men in the lowest quartile of HDL2-mass were not to the lowest quartile of HDL-cholesterol or The current analyses that the risk for premature fatal CHD ≤ 65 years) was over and for total fatal 63% greater for men who in the lowest HDL quartile higher the Prospective Cardiovascular reported a greater coronary disease risk for with HDL-cholesterol levels ≤ mg/dl higher HDL-cholesterol G. H. A. Y. lipoprotein cholesterol as a of coronary heart disease risk. The and for cholesterol Full Text PDF PubMed Scopus Google to be The analyses of the the Lipid the and the Risk suggest a in mg/dl in HDL-cholesterol CHD risk by in men and in women J.D. J.D. S. H.A. lipoprotein cholesterol and cardiovascular prospective PubMed Scopus Google Scholar). HDL-cholesterol and the lowest quartile of HDL2-mass the 25th HDL the is less the relationship reported for total HDL-cholesterol by J.D. J.D. S. H.A. lipoprotein cholesterol and cardiovascular prospective PubMed Scopus Google Scholar) was not in the higher of the HDL2-mass distribution in their the does 28% of the The in the analytic ultracentrifuge measurements was to the more traditional measurements of lipids and lipoprotein cholesterol, analyses showed that the for measurements in and P.D. Stefanick M.L. P.T. The effects on plasma lipoproteins of a with or in men and Engl. J. Med. 1991; 325: PubMed Scopus Google Scholar, P.D. Stefanick M.L. B. P.T. Vranizan K.M. in plasma lipids and lipoproteins in men during through as compared with Engl. J. Med. PubMed Scopus Google Scholar) measured one were for HDL2-mass for for for for LDL-mass and for for and for small and for for The association for the analytic ultracentrifuge measurements is to the between lipoprotein subfractions and the results the risk 2 two by Gofman and i) analytic ultracentrifuge measurements of lipoproteins were to CHD and ii) lipoproteins for serum relationship to In the of of and was to in men the analytic lipoprotein measurements were a of than total serum cholesterol levels J.W. M. L.A. of serum lipoprotein and cholesterol measurements as of clinical of report of a study of lipoproteins and Google Scholar). The with in and in measurements had the of with Gofman's during the a in for at that the other were to due to or The was that CHD was to small and total cholesterol not and that cholesterol was more predictive of CHD than were The of over total cholesterol in their with the between and Gofman a new prospective study of Livermore (3Gofman J.W. Young W. Tandy R. Ischemic heart disease, atherosclerosis, and longevity.Circulation. 1966; 34: 679-697Crossref PubMed Scopus (423) Google Scholar). In 1966, reported when compared with serum concentrations of the total the 38 men who developed clinical ischemic heart disease during 10 of follow-up had 32% lower HDL2 (P < 8% lower HDL3 (P= 0.02), higher (P < 0.001), higher (P < 0.001), and higher small (P < (3Gofman J.W. Young W. Tandy R. Ischemic heart disease, atherosclerosis, and longevity.Circulation. 1966; 34: 679-697Crossref PubMed Scopus (423) Google Scholar). 2 that 53 of low HDL2, low HDL3, and levels of and small increased CHD risk and that for LDL-mass concentrations the of total cholesterol as a CHD risk in The current with analyses (17Williams P.T. Feldman D.E. Prospective study of coronary heart disease vs. HDL2, HDL3, and other lipoproteins in Gofman's Livermore Cohort.Atherosclerosis. 2011; 214: 196-202Abstract Full Text Full Text PDF PubMed Scopus (77) Google for a independent of low HDL2-mass by ultracentrifugation with HDL-cholesterol in predicting CHD and limitations to these is on the study in Gofman's report on the In the lipoprotein measurements were may be a or M. P. A. and risk of myocardial ischemic heart disease, and death in men and AMA. PubMed Scopus Google Scholar, S. Buring J.E. Rifai N. S. Sacks F.M. Ridker P.M. compared with and risk of cardiovascular in AMA. PubMed Scopus Google Scholar). the were the predictive of risk factors for including the risk to be for other when for risk levels and disease (11Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in AdultsExecutive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).J AMA. 2001; 285: 2486-2497Crossref PubMed Scopus (24245) Google Scholar). the analytic ultracentrifuge is not for routine measurements of lipoprotein subfractions, the of these analyses is to the of the lipoprotein concentrations than a for their measurements. In these analyses for the clinical of low HDL2 in predicting fatal The association between HDL2 and CHD may not be The of Lipid to in higher all-cause mortality in patients HDL-cholesterol levels were by of P.J. M. M. M. J. L. of in patients at high risk for coronary Engl. J. Med. PubMed Scopus Google Scholar). The HDL2 particles in these patients G. B. N. W. M. the activities of HDL2 and HDL3 particles in the cholesterol Thromb. Vasc. Biol. 2009; PubMed Scopus Google Scholar). The between clinical results and suggest a to more the HDL2 or the to low HDL2 that for association with CHD risk. with mass coronary heart disease
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".