@article{rashid_sniderman_melone_brown_otvos_mente_schulze_mcqueen_anand_yusuf_2015, title={Elevated cholesteryl ester transfer protein (CETP) activity, a major determinant of the atherogenic dyslipidemia, and atherosclerotic cardiovascular disease in South Asians}, volume={22}, ISSN={["2047-4881"]}, DOI={10.1177/2047487314528461}, abstractNote={Aims Why South Asians are at increased risk of premature atherosclerotic cardiovascular diseases compared with other ethnic groups is not fully understood. Atherogenic dyslipoproteinemia – hypertriglyceridemia, elevated numbers of low-density lipoprotein (LDL) particles and low high-density lipoprotein cholesterol (HDL-C) – is more common in South Asians but the mechanisms responsible have not been explicated. Here we examined whether the circulating lipid transfer protein, cholesteryl ester transfer protein (CETP), plays a role in the pathogenesis of the atherogenic dyslipoproteinemia among South Asians. Methods and results CETP activity was determined by exogenous substrate assay in the serum of healthy, metabolically well-characterized individuals of South Asian and European descent (N = 244 and 238, respectively). Serum and lipoprotein lipids and apolipoproteins were measured and lipoprotein particle number and size were quantified via nuclear magnetic resonance spectroscopy. All the elements of the atherogenic dyslipoproteinemia were more severe in South Asians and CETP activity was significantly greater by 30% in South Asians compared with Europeans, adjusted for age, sex, body mass index and waist circumference (p < 0.0001). CETP activity was directly associated with serum triglycerides and inversely with HDL-C in the whole population. CETP activity was also directly related to apoB and LDL particle number. Finally, increased CETP activity was associated with pro-atherogenic reductions in HDL and LDL particle size. Conclusions We identified novel associations between elevated CETP activity and the triad of quantitative and qualitative lipoprotein abnormalities in the atherogenic dyslipidemia in South Asians, a major contributor of increased atherosclerotic cardiovascular diseases in South Asians.}, number={4}, journal={EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY}, author={Rashid, Shirya and Sniderman, Allan and Melone, Michelle and Brown, Patrick E. and Otvos, James D. and Mente, Andrew and Schulze, Karleen and McQueen, Matthew J. and Anand, Sonia S. and Yusuf, Salim}, year={2015}, month={Apr}, pages={468–477} }
 @article{ruano_seip_windemuth_zollner_tsongalis_ordovas_otvos_bilbie_miles_zoeller_et al._2006, title={Apolipoprotein A1 genotype affects the change in high density lipoprotein cholesterol subfractions with exercise training}, volume={185}, ISSN={["0021-9150"]}, DOI={10.1016/j.atherosclerosis.2005.05.029}, abstractNote={High density lipoprotein cholesterol (HDL-C) is a primary risk factor for cardiovascular disease. Apolipoprotein A-1 (apoA1) is the major HDL-associated apolipoprotein. The -75G/A single nucleotide polymorphism (SNP) in the apolipoprotein A1 gene (APOA1) promoter has been reported to be associated with HDL-C concentrations as well as HDL-C response to dietary changes in polyunsaturated fat intake. We examined the effect of this APOA1 SNP on exercise-induced changes in HDL subfraction distribution. From a cohort of healthy normolipidemic adults who volunteered for 6 months of supervised aerobic exercise, 75 subjects were genotyped for the -75G/A SNP. Of these, 53 subjects were G homozygotes (G/G) and 22 were A carriers (A/G and A/A). HDL subfractions were measured by nuclear magnetic resonance (NMR) spectroscopy by adding categories HDL-C 1+2 for the small subfraction, and HDL-C 3+4+5 for the large. The change in total HDL-C after exercise was 0.8+/-7.2 mg/dL (+1.7%), and was not statistically significant. HDL subfraction amounts also did not significantly change with exercise training in the total cohort or in G homozygotes or A carriers. The amount of the large HDL subfraction increased in the G homozygotes and decreased in the A carriers (mean+/-S.E.M., 1.8+/-6.6 mg/dL versus -6.1+/-2.3 mg/dL, p<0.0005). In contrast, the amount of the small HDL subfraction decreased in G homozygotes and increased in A carriers (-1.3+/-6.6 mg/dL versus 4.7+/-1.2 mg/dL, p<0.005). These results show that genetic variation at the APOA1 gene promoter is associated with HDL subfraction redistribution resulting from exercise training.}, number={1}, journal={ATHEROSCLEROSIS}, author={Ruano, G and Seip, RL and Windemuth, A and Zollner, S and Tsongalis, GJ and Ordovas, J and Otvos, J and Bilbie, C and Miles, M and Zoeller, R and et al.}, year={2006}, month={Mar}, pages={65–69} }
 @article{nuclear magnetic resonance-determined lipoprotein subclass profile in the dcct/edic cohort: associations with carotid intima-media thickness_2006, volume={23}, number={9}, journal={Diabetic Medicine: A Journal of the British Diabetic Association}, year={2006}, pages={955–966} }
 @article{seip_otvos_bilbie_tsongalis_miles_zoeller_visich_gordon_angelopoulos_pescatello_et al._2006, title={The effect of apolipoprotein E genotype on serum lipoprotein particle response to exercise}, volume={188}, ISSN={["0021-9150"]}, DOI={10.1016/j.atherosclerosis.2005.06.050}, abstractNote={Exercise affects lipoprotein metabolism and apolipoprotein E (Apo E) genotype may alter changes in lipoprotein subclasses that occur with exercise. The present study examined the effects of Apo E genotype (APOE) on the response of lipoprotein subclass concentrations to long-term exercise. A prospective longitudinal study, conducted at seven centers, genetically screened 566 individuals to create three cohorts of healthy adults, equal for gender and the most common APOE variants: E2/3 (n = 35), E3/3 (n = 40), and E3/4 (n = 31). Subjects with body mass index (BMI) > or = 31 or evidence of dyslipidemia or metabolic disease were excluded. All subjects exercised aerobically at 75% of maximal heart rate for 40 min, four times weekly for 6 months. Fasting lipoprotein subpopulations were measured before and after exercise training using proton nuclear magnetic resonance spectroscopy. Serum lipids for the entire cohort did not change with exercise training, but the LDL subpopulation response varied by APOE. Small-sized LDL particles decreased only in the APOE3 homozygotes whereas medium-sized LDL particles increased only in this group. These changes were directionally different from the responses in the E2/3 and E3/4 subjects (p < 0.05). Neither exercise nor APOE variant affected overall LDL or HDL size or cholesterol concentration, but exercise decreased VLDL diameter by 3.5 nm (p < 0.001) attributable to decreases in large VLDL in each APOE group. In conclusion, APOE variants influence the serum LDL subpopulation response to exercise training in normolipidemic subjects. Subjects homozygous for APOE3 experienced the most beneficial lipid effects from exercise training.}, number={1}, journal={ATHEROSCLEROSIS}, author={Seip, Richard L. and Otvos, James and Bilbie, Cherie and Tsongalis, Gregory J. and Miles, Mary and Zoeller, Robert and Visich, Paul and Gordon, Paul and Angelopoulos, Theodore J. and Pescatello, Linda and et al.}, year={2006}, month={Sep}, pages={126–133} }
 @article{kuivenhoven_hovingh_tol_jauhiainen_ehnholm_fruchart_brinton_otvos_smelt_brownlee_et al._2003, title={Heterozygosity for ABCA1 gene mutations: effects on enzymes, apolipoproteins and lipoprotein particle size}, volume={171}, ISSN={["0021-9150"]}, DOI={10.1016/j.atherosclerosis.2003.08.014}, abstractNote={A cohort of 13 female and 14 male heterozygotes for ATP binding cassette A1 (ABCA1) gene defects was directly compared with 13 and 14 unaffected female and male family members of almost exact same age. The activities of three proteins that play key roles in HDL metabolism were measured in addition to extensive lipid and (apo) lipoprotein subfraction analysis. Compared to controls, LCAT activity was reduced by 15% in affected subjects (P<0.001) while PLTP activity was unaffected. Interestingly, CETP activity was elevated by 50% in the heterozygote siblings of one kindred but was unaffected in heterozygotes of the three other families. With respect to lipids, the heterozygotes had normal total cholesterol (TC), and LDL-cholesterol concentrations but presented with a trend towards increased triglyceride levels (13%; P=0.08). HDL metabolism, by contrast, was severely affected as illustrated by 40% reductions in HDL-cholesterol (P<0.001) with concomitant reductions in apoAI (25%; P<0.001) levels and in lipoprotein subfraction LpAI (28%; P<0.001), LpAI:AII (24%; P=0.014), and LpCIII:nonB (34%; P<0.001) concentrations. We furthermore observed reduced average HDL particle size (5%; P=0.004; 16% in female and 3.6% in male) and reduced plasma apoCIII concentration (15%; P=0.006) while apoAII, apoAIV, apoE and apoB levels were unchanged. In conclusion, heterozygosity for ABCA1 defects was associated with reduced LCAT activity in absence of effects on PLTP activity. Of special interest was our finding that the effects of compromised ABCA1 function on HDL were more pronounced in women than in men.}, number={2}, journal={ATHEROSCLEROSIS}, author={Kuivenhoven, JA and Hovingh, GK and Tol, A and Jauhiainen, M and Ehnholm, C and Fruchart, JC and Brinton, EA and Otvos, JD and Smelt, AHM and Brownlee, A and et al.}, year={2003}, month={Dec}, pages={311–319} }
 @article{jenkins_lyons_zheng_otvos_lackland_mcgee_garvey_klein_2003, title={Lipoproteins in the DCCT/EDIC cohort: Associations with diabetic nephropathy}, volume={64}, ISSN={["1523-1755"]}, DOI={10.1046/j.1523-1755.2003.00164.x}, abstractNote={BACKGROUND
Lipoproteins may contribute to diabetic nephropathy. Nuclear magnetic resonance (NMR) can quantify subclasses and mean particle size of very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL), and LDL particle concentration. The relationship between detailed lipoprotein analyses and diabetic nephropathy is of interest.


METHODS
In a cross-sectional study, lipoproteins from 428 women and 540 men from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort were characterized by conventional lipid enzymology, NMR, apolipoprotein levels, and LDL oxidizibility. Linear regression was performed for each lipoprotein parameter versus log albumin excretion rate (AER), with and without covariates for age, diabetes duration, HbA1c, hypertension, body mass index, waist-hip ratio, and DCCT treatment group. Significance was taken at P < 0.05.


RESULTS
By multivariate analysis, conventional profile, total triglycerides, total- and LDL cholesterol, but not HDL cholesterol, were associated with AER. NMR-determined large, medium, and small VLDL were associated with AER in both genders (except large VLDL in women), and intermediate density lipoprotein (IDL) was associated with AER (men only). LDL particle concentration and ApoB were positively associated with AER (in men and in the total cohort), and there was a borderline inverse association between LDL diameter and AER in men. Small HDL was positively associated with AER and a borderline negative association was found for large HDL. No associations were found with ApoA1, Lp(a), or LDL oxidizibility.


CONCLUSION
Potentially atherogenic lipoprotein profiles are associated with renal dysfunction in type 1 diabetes and further details are gained from NMR analysis. Longitudinal studies are needed to determine if dyslipoproteinemia can predict patients at risk of nephropathy, or if lipoprotein-related interventions retard nephropathy.}, number={3}, journal={KIDNEY INTERNATIONAL}, author={Jenkins, AJ and Lyons, TJ and Zheng, DY and Otvos, JD and Lackland, DT and McGee, D and Garvey, WT and Klein, RL}, year={2003}, month={Sep}, pages={817–828} }
 @misc{otvos_jeyarajah_shalaurova_2003, title={Method of determining presence and concentration of lipoprotein X in blood plasma and serum}, volume={6,617,167}, number={2003 Sept. 9}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Otvos, J. and Jeyarajah, E. and Shalaurova, I.}, year={2003} }
 @misc{otvos_bennett_2003, title={Methods and computer program products for determining risk of developing type 2 diabetes and other insulin resistance related disorders}, volume={6,518,069}, number={2003 Feb. 11}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Otvos, J. D. and Bennett, D. W.}, year={2003} }
 @misc{otvos_2003, title={Methods for providing personalized lipoprotein-based risk assessments}, volume={6,653,140}, number={2003 Nov. 25}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Otvos, J.}, year={2003} }
 @misc{otvos_2003, title={Methods, systems, and computer program products for analyzing and presenting NMR lipoprotein-based risk assessment results}, volume={6,576,471}, number={2003 June 10}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Otvos, J.}, year={2003} }
 @article{jenkins_lyons_zheng_otvos_lackland_mcgee_garvey_klein_2003, title={Serum lipoproteins in the diabetes control and complications trial/epidemiology of diabetes intervention and complications cohort - Associations with gender and glycemia}, volume={26}, ISSN={["1935-5548"]}, DOI={10.2337/diacare.26.3.810}, abstractNote={OBJECTIVE—To relate the nuclear magnetic resonance (NMR)-determined lipoprotein profile, conventional lipid and apolipoprotein measures, and in vitro oxidizibility of LDL with gender and glycemia in type 1 diabetes.}, number={3}, journal={DIABETES CARE}, author={Jenkins, AJ and Lyons, T and Zheng, DY and Otvos, JD and Lackland, DT and McGee, D and Garvey, WT and Klein, RL}, year={2003}, month={Mar}, pages={810–818} }
 @article{brousseau_jj o'connor_ordovas_collins_otvos_massov_mcnamara_rubins_robins_schaefer_2002, title={Cholesteryl ester transfer protein TaqI B2B2 genotype is associated with higher HDL cholesterol levels and lower risk of coronary heart disease end points in men with HDL deficiency - Veterans Affairs HDL Cholesterol Intervention Trial}, volume={22}, ISSN={["1079-5642"]}, DOI={10.1161/01.ATV.0000024566.57589.2E}, abstractNote={
            
              
                
                  Objective
                
                —
              
            
            We have previously reported that genetic variation at the cholesteryl ester transfer protein (CETP)
            Taq
            IB locus is correlated with plasma lipid levels and coronary heart disease (CHD) risk in the Framingham Offspring Study (FOS). In FOS, the B2 allele was associated with increased levels of high density lipoprotein (HDL) cholesterol (HDL-C), decreased CETP activity, and reduced CHD risk for men having the B2B2 genotype. The present study was undertaken to further define the relationship between this polymorphism and CHD risk at the population level.
          }, number={7}, journal={ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY}, author={Brousseau, ME and JJ O'Connor and Ordovas, JM and Collins, D and Otvos, JD and Massov, T and McNamara, JR and Rubins, HB and Robins, SJ and Schaefer, EJ}, year={2002}, month={Jul}, pages={1148–1154} }
 @article{otvos_shalaurova_freedman_rosenson_2002, title={Effects of pravastatin treatment on lipoprotein subclass profiles and particle size in the PLAC-I trial}, volume={160}, ISSN={["0021-9150"]}, DOI={10.1016/S0021-9150(01)00544-5}, abstractNote={Lipoprotein subclass analyses may facilitate coronary heart disease (CHD) risk stratification and provide insight into the cardioprotective benefits of statins (3-hydroxymethylglutaryl-coenzyme A reductase inhibitors). This study evaluated the influence of pravastatin on lipoprotein subclass profiles to determine whether subjects with predominantly large LDL (LDL size >20.5 nm) or small LDL (LDL size ≤20.5 nm) at baseline differ in responsiveness to drug treatment. Frozen plasma specimens were analyzed from a subset of participants in the Pravastatin Limitation of Atherosclerosis in the Coronaries (PLAC-I) trial at baseline and after treatment for 6 months with pravastatin (n=154) or placebo (n=138). Lipids were measured by standard chemical methods and lipoprotein subclasses by nuclear magnetic resonance (NMR) spectroscopy. Pravastatin-induced changes in lipid levels were similar in subjects with large or small LDL at baseline. Levels of the most abundant LDL subclass were preferentially lowered by pravastatin, resulting in an increase in average LDL size for those with a predominance of small LDL. High-risk CHD subjects with small LDL particles gain at least as much pharmacological benefit from pravastatin as those with large LDL, as evidenced by reductions in the numbers of total and small LDL particles, and increases in average LDL and HDL particle size.}, number={1}, journal={ATHEROSCLEROSIS}, author={Otvos, JD and Shalaurova, I and Freedman, DS and Rosenson, RS}, year={2002}, month={Jan}, pages={41–48} }
 @article{humphries_berglund_isasi_otvos_kaluski_deckelbaum_shea_talmud_2002, title={Loci for CETP, LPL, LIPC, and APOC3 affect plasma lipoprotein size and subpopulation distribution in Hispanic and non- Hispanic white subjects: the Columbia University BioMarkers Study}, volume={12}, number={4}, journal={Nutrition, Metabolism, and Cardiovascular Diseases}, author={Humphries, S. E. and Berglund, L. and Isasi, C. R. and Otvos, J. D. and Kaluski, D. and Deckelbaum, R. and Shea, S. and Talmud, P.}, year={2002}, pages={163–172} }
 @article{rosenson_otvos_freedman_2002, title={Relations of lipoprotein subclass levels and low-density lipoprotein size to progression of coronary artery disease in the pravastatin limitation of atherosclerosis in the coronary arteries (PLAC-I) trial}, volume={90}, ISSN={["0002-9149"]}, DOI={10.1016/S0002-9149(02)02427-X}, abstractNote={Lipoprotein subclass measurements may enhance the prediction of coronary artery disease (CAD) risk, but clinical application of such information has been hindered by the relatively laborious and time-consuming nature of laboratory measurement methods. In this study, lipoprotein subclass analyses were performed on frozen plasma samples from 241 participants in the Pravastatin Limitation of Atherosclerosis in the Coronary arteries Trial using an automated nuclear magnetic resonance technique. The objective was to determine if levels of these subclasses provided additional information on the progression of CAD, based on the change in the minimum lumen diameter, over a 3-year period. After adjustment for race, sex, age, treatment group, baseline lumen diameter, and chemically measured levels of triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol, on-trial predictors (p <0.05) of progression included an elevated LDL particle number, and levels of small LDL and small HDL. Within treatment groups, CAD progression was most strongly related to the LDL particle number (placebo) and levels of small HDL (pravastatin). In logistic regression models that adjusted for chemically determined lipid levels and other covariates, a small LDL level > or = 30 mg/dl (median) was associated with a ninefold increased risk of CAD progression (p <0.01) in the placebo group. These results indicate that levels of various lipoprotein subclasses may provide useful information on CAD risk even if levels of traditional risk factors are known.}, number={2}, journal={AMERICAN JOURNAL OF CARDIOLOGY}, author={Rosenson, RS and Otvos, JD and Freedman, DS}, year={2002}, month={Jul}, pages={89–94} }
 @article{galluzzi_cupples_otvos_wilson_schaefer_ordovas_2001, title={Association of the A/T54 polymorphism in the intestinal fatty acid binding protein with variations in plasma lipids in The Framingham Offspring Study}, volume={159}, ISSN={["1879-1484"]}, DOI={10.1016/S0021-9150(01)00517-2}, abstractNote={We investigated the potential role of the genetic variation at the intestinal fatty acid binding protein gene (FABP2) in influencing lipid levels in a representative sample of the Framingham Offspring Study participants (n=1930). In men, the T54 allele was associated with significantly higher LDL-cholesterol (3.47+/-0.83 vs. 3.36+/-0.83 mmol/l; P<0.047), and ApoB (1.04+/-0.23 vs. 1.01+/-0.24 g/l; P<0.020) after adjustment for familial relationship, age, BMI, smoking, alcohol intake and the use of beta-blockers compared with the A54 allele. This relationship with ApoB continued to be significant after adjustment for APOE genotype (P<0.034). In women, the T54 allele was associated with significantly higher total-cholesterol (5.32+/-1.01 vs. 5.17+/-0.98 mmol/l; P<0.049) and LDL-cholesterol (3.31+/-0.93 vs. 3.18+/-0.85 mmol/l; P<0.023) after adjustment for covariates and menopausal status, estrogen therapy and APOE genotype. In men, the T54 allele was associated with significantly higher levels of small VLDL and lower levels of large HDL. Moreover, there was no significant relationship between FABP2 alleles and lipoprotein diameter or the prevalence of coronary heart disease in both genders. Our data are consistent with the T54 IFABP increasing the flux of lipids through the enterocyte leading to an increase in chylomicron secretion.}, number={2}, journal={ATHEROSCLEROSIS}, author={Galluzzi, JR and Cupples, LA and Otvos, JD and Wilson, PWF and Schaefer, EJ and Ordovas, JM}, year={2001}, month={Dec}, pages={417–424} }
 @article{russo_meigs_cupples_demissie_otvos_wilson_lahoz_cucinotta_couture_mallory_et al._2001, title={Association of the Sst-I polymorphism at the APOC3 gene locus with variations in lipid levels, lipoprotein subclass profiles and coronary heart disease risk: the Framingham offspring study}, volume={158}, ISSN={["0021-9150"]}, DOI={10.1016/S0021-9150(01)00409-9}, abstractNote={Apolipoprotein (apo) CIII participates in the regulation of the metabolism of triglyceride-rich lipoproteins and it is a major component of chylomicrons and VLDL. The APOC3 gene is on chromosome 11q23 and is highly polymorphic. The less common allele (S2) of the SstI polymorphism on the 3' untranslated region of the APOC3 gene has been previously associated with increased triglycerides, total cholesterol (TC), and apoCIII levels and cardiovascular risk on several, but not all, studies. The aim of this study was to examine the association of this polymorphism with plasma lipid levels, lipoprotein subfractions and coronary heart disease (CHD) risk in a population-based study: The Framingham Offspring Study. The frequency of the S2 allele was 0.086, consistent with previous reports in Caucasian populations. In men, the S2 allele was associated with lower concentrations of high-density lipoprotein cholesterol (HDL-C; P<0.04) and HDL2-C (P<0.02) and a significant increase in apoCIII non-HDL (P<0.05). TG levels were higher in men carriers of the S2 allele, but this association did not reach statistical significance (P=0.30). Conversely, in women, the S2 allele was associated with increased TC (P<0.03), low-density lipoprotein cholesterol (LDL-C; P<0.03), and ApoB levels (P<0.04). Lipoproteins subfractions were also examined using nuclear magnetic resonance (NMR) spectroscopy. S2 male carriers had significantly lower concentrations of large LDL and a significant reduction in LDL particle size (P<0.04). In women, there was a significant increase in intermediate LDL particles (P<0.05) with no significant effect on lipoprotein diameters. We also examined the associations between the S2 allele and biochemical markers of glucose metabolism. In men, the S2 allele was associated with elevated fasting insulin concentrations (P<0.04), whereas no significant associations were observed in women. Despite the described associations with lipid and glucose metabolism related risk factors, we did not find any significant increase in CHD risk associated with the S2 allele in this population.}, number={1}, journal={ATHEROSCLEROSIS}, author={Russo, GT and Meigs, JB and Cupples, LA and Demissie, S and Otvos, JD and Wilson, PWF and Lahoz, C and Cucinotta, D and Couture, P and Mallory, T and et al.}, year={2001}, month={Sep}, pages={173–181} }
 @article{freedman_bowman_srinivasan_berenson_otvos_2001, title={Distribution and correlates of high-density lipoprotein subclasses among children and adolescents}, volume={50}, ISSN={["1532-8600"]}, DOI={10.1053/meta.2001.21027}, abstractNote={Levels of high-density lipoprotein (HDL) cholesterol among children vary by sex and race/ethnicity and are correlated with age, obesity, and other characteristics. Several studies of adults have indicated that atherogenicity of HDL particles may vary by size, but there is little information on the distribution and correlates of HDL subfractions in early life. We used nuclear magnetic resonance (NMR) spectroscopy to determine the mean HDL particle size and levels of 3 HDL subclasses among 10- to 17-year-olds (n = 918). We found the mean HDL particle size to be (1) inversely associated with age among boys, (2) larger among girls than boys, and (3) larger among black children than among white children. These associations with particle size reflected contrasting associations with various HDL subclasses; among boys, for example, levels of large HDL decreased with age, whereas levels of small HDL remained constant (black boys) or tended to increase (white boys). Furthermore, relative weight and levels of both triglycerides and low-density lipoprotein (LDL) cholesterol were associated inversely with levels of large HDL, but positively with levels of small HDL. These contrasting associations suggest that the role of HDLC in coronary heart disease (CHD) may be more complex than previously thought, and that the analysis of HDL subclasses may improve the accuracy of CHD prediction.}, number={3}, journal={METABOLISM-CLINICAL AND EXPERIMENTAL}, author={Freedman, DS and Bowman, BA and Srinivasan, SR and Berenson, GS and Otvos, JD}, year={2001}, month={Mar}, pages={370–376} }
 @article{miller_dolinar_cromwell_otvos_2001, title={Effectiveness of high doses of Simvastatin as monotherapy in mixed hyperlipidemia}, volume={87}, ISSN={["1879-1913"]}, DOI={10.1016/S0002-9149(00)01327-8}, abstractNote={Twenty subjects with mixed hyperlipidemia participated in a 3-arm crossover trial to evaluate the effectiveness of high-dose simvastatin as monotherapy. Significant reductions were observed in atherogenic lipids and lipoproteins. The highest dose of simvastatin also resulted in significant increases in high-density lipoprotein cholesterol (21%) with a comparable increase in large, protective high-density lipoprotein particles.}, number={2}, journal={AMERICAN JOURNAL OF CARDIOLOGY}, author={Miller, M and Dolinar, C and Cromwell, W and Otvos, JD}, year={2001}, month={Jan}, pages={232-+} }
 @article{tangney_mosca_otvos_rosenson_2001, title={Oral 17 beta-estradiol and medroxyprogesterone acetate therapy in postmenopausal women increases HDL particle size}, volume={155}, ISSN={["0021-9150"]}, DOI={10.1016/s0021-9150(00)00577-3}, abstractNote={Menopause is accompanied by changes in lipoprotein particles that include an increase in density of low density lipoproteins (LDL) and high density lipoproteins (HDL) particles. The effect of 3 months of oral hormone replacement therapy (HRT) on lipoprotein particle size in postmenopausal women who were randomized to (1) estrogen replacement therapy (ERT) alone (either 17beta-estradiol (1 mg) or conjugated equine estrogens (CEE) (0.625 mg); (2) combination therapy (17beta-estradiol plus medroxyprogesterone acetate (MPA) or CEE plus MPA); and (3) placebo were examined. Lipoprotein subclass concentrations and particle size were quantified by nuclear magnetic resonance spectroscopy (NMR). Combination HRT resulted in significant (P=0.002) increases in HDL particle size as compared with those on placebo formulations or ERT alone. Women assigned to combined HRT had lower concentrations of smaller HDL particles after 3 months (P=0.005) and higher concentrations of larger HDL particles (P=0.02), whereas women assigned to ERT or placebo experienced non-significant changes. In summary, combined HRT increases HDL particle size by altering concentrations of the smallest and largest HDL subspecies.}, number={2}, journal={ATHEROSCLEROSIS}, author={Tangney, CC and Mosca, LJ and Otvos, JD and Rosenson, RS}, year={2001}, month={Apr}, pages={425–430} }
 @article{zangger_shen_oz_otvos_armitage_2001, title={Oxidative dimerization in metallothionein is a result of intermolecular disulphide bonds between cysteines in the alpha- domain}, volume={359}, number={2001 Oct 15}, journal={Biochemical Journal (London, England : 1984)}, author={Zangger, K. and Shen, G. and Oz, G. and Otvos, J. D. and Armitage, I. M.}, year={2001}, pages={353–360} }
 @article{couture_otvos_cupples_wilson_schaefer_ordovas_2000, title={Absence of association between genetic variation in the promoter of the microsomal triglyceride transfer protein gene and plasma lipoproteins in the Framingham Offspring Study}, volume={148}, ISSN={["0021-9150"]}, DOI={10.1016/S0021-9150(99)00281-6}, abstractNote={Microsomal triglyceride transfer protein (MTP) is a lipid transfer protein that is required for the assembly and secretion of very low density lipoproteins (VLDL) by the liver and chylomicrons by the intestine. The common G-493T polymorphism of the MTP promoter has been shown to be associated with decreased plasma LDL-cholesterol and ApoB content of VLDL. The purpose of the present study was, therefore, to investigate the association of this mutation with variations in lipid and apoprotein levels, lipoprotein subclass profiles and coronary heart disease (CHD) risk in a population-based sample of 1226 male and 1284 female Framingham Offspring participants. In men and women, no significant association was found between the G-493T MTP polymorphism and variations of plasma levels of total cholesterol, LDL-cholesterol, apoprotein B, HDL-cholesterol, apoprotein AI and triglycerides. In order to further investigate potential relationships with variations of lipoprotein phenotypes, lipoprotein subclass profiles were measured using automated nuclear magnetic resonance (NMR) spectroscopy. Each NMR profile yielded information on lipid mass of VLDL, LDL, and HDL subclasses. In both genders, there was no significant association between the G-493T polymorphism and variability of lipoprotein subclass distributions or lipoprotein particle size. Furthermore, no significant association was found between the polymorphism of the MTP promoter and prevalence or the age of onset of CHD. Thus, our results suggest that the G-493T mutation in the MTP promoter is unlikely to have significant implications for cardiovascular disease in men and women.}, number={2}, journal={ATHEROSCLEROSIS}, author={Couture, P and Otvos, JD and Cupples, LA and Wilson, PWF and Schaefer, EJ and Ordovas, JM}, year={2000}, month={Feb}, pages={337–343} }
 @article{isasi_shea_deckelbaum_couch_starc_otvos_berglund_2000, title={Apolipoprotein epsilon 2 allele is associated with an anti-atherogenic lipoprotein profile in children: The Columbia University BioMarkers Study}, volume={106}, ISSN={["0031-4005"]}, DOI={10.1542/peds.106.3.568}, abstractNote={
                  Objective.
                  We examined associations between allelic variation in the apo ε gene, which codes for apolipoprotein E, and plasma lipid levels in children.
               }, number={3}, journal={PEDIATRICS}, author={Isasi, CR and Shea, S and Deckelbaum, RJ and Couch, SC and Starc, TJ and Otvos, JD and Berglund, L}, year={2000}, month={Sep}, pages={568–575} }
 @article{ordovas_cupples_corella_otvos_osgood_martinez_lahoz_coltell_wilson_schaefer_2000, title={Association of cholesteryl ester transfer protein-TaqIB polymorphism with variations in lipoprotein subclasses and coronary heart disease risk - The Framingham study}, volume={20}, ISSN={["1079-5642"]}, DOI={10.1161/01.ATV.20.5.1323}, abstractNote={
            Abstract
            —Cholesteryl ester transfer protein (CETP) facilitates the exchange of triglycerides and cholesteryl esters between lipoprotein particles, a key step in reverse cholesterol transport in humans. Variations at the CETP locus have been shown to be determinants of the levels and activity of CETP and high density lipoprotein (HDL) plasma concentration. The associations of the common CETP polymorphism,
            Taq
            IB in intron 1, with lipoprotein levels and particle size distribution, CETP activity, and coronary heart disease (CHD) risk were examined in a population-based sample of 1411 men and 1505 women from the Framingham Offspring Study. The B2 allele frequency was 0.444 in men and 0.433 in women, and its presence was significantly (
            P
            <0.05) associated with decreased CETP activity. B1B1 men had lower HDL cholesterol (HDL-C) levels (1.07 mmol/L) compared with B1B2 (1.14 mmol/L) and B2B2 (1.18 mmol/L) men (
            P
            <0.001). Likewise, B1B1 women had lower HDL-C levels (1.40 mmol/L) compared with B1B2 (1.46 mmol/L) and B2B2 (1.53 mmol/L) women (
            P
            <0.001). In men, the B2 allele was associated with increased particle size for HDL and low density lipoprotein. In women, a similar effect was demonstrated only for HDL particle size. The odds ratio for prevalent CHD associated with the B2 allele was 0.696 (
            P
            =0.035) in men. After adjusting for age, body mass index, systolic blood pressure, diabetes, smoking, alcohol consumption, β-blocker use, total cholesterol, and HDL-C, this odds ratio was 0.735 (
            P
            =0.187), suggesting that the protective effect of the B2 allele was due in part to its association with HDL-C levels. No significant protective effects were observed in women. These data demonstrate that variation at the CETP gene locus is a significant determinant of HDL-C levels, CETP activity, and lipoprotein size in this population. Moreover, these effects appear to translate into a lower CHD risk among those men with the B2 allele.
          }, number={5}, journal={ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY}, author={Ordovas, JM and Cupples, LA and Corella, D and Otvos, JD and Osgood, D and Martinez, A and Lahoz, C and Coltell, O and Wilson, PWF and Schaefer, EJ}, year={2000}, month={May}, pages={1323–1329} }
 @article{couture_otvos_cupples_lahoz_wilson_schaefer_ordovas_2000, title={Association of the C-514T polymorphism in the hepatic lipase gene with variations in lipoprotein subclass profiles - The Framingham Offspring Study}, volume={20}, ISSN={["1079-5642"]}, DOI={10.1161/01.ATV.20.3.815}, abstractNote={
            Abstract
            —Hepatic lipase is involved in the metabolism of several lipoproteins and has a key role in reverse cholesterol transport. A common C-to-T substitution at position −514 of the hepatic lipase promoter has been associated with variations in plasma high density lipoprotein cholesterol (HDL-C) levels and hepatic lipase activity. The aim of the current study was to investigate the association of this polymorphism to lipoprotein levels in a population-based sample of 1314 male and 1353 female Framingham Offspring Study participants. In men and women, carriers of the −514
            T
            allele had higher HDL-C and apolipoprotein A-I (apoAI) concentrations compared with noncarriers. The higher HDL-C levels associated with the −514
            T
            allele was due to an increase in the HDL
            2
            -C subfraction, and this association was stronger in women compared with men (
            P
            =0.0043 versus 0.0517). To gain further understanding about the metabolic basis of these effects, HDL and low density lipoprotein (LDL) subclass profiles were measured by using automated nuclear magnetic resonance spectroscopy and gradient gel electrophoresis, respectively. The association of the −514
            T
            allele with higher HDL-C levels seen in men and women was primarily due to significant increases in the large HDL subfractions (size range 8.8 to 13.0 nm). In contrast, there was no relationship between the hepatic lipase polymorphism at position −514 and the LDL particle size distribution after adjustment for familial relationships, age, body mass index, smoking, alcohol intake, use of β-blockers, apoE genotype, and menopausal status and estrogen therapy in women. Moreover, multiple regression analyses suggested that the C−514T polymorphism contributed significantly to the variability of HDL particle size in men and women (
            P
            <0.04). Thus, our results show that the C−514T polymorphism in the hepatic lipase gene is associated with significant variations in the lipoprotein profile in men and women.
          }, number={3}, journal={ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY}, author={Couture, P and Otvos, JD and Cupples, LA and Lahoz, C and Wilson, PWF and Schaefer, EJ and Ordovas, JM}, year={2000}, month={Mar}, pages={815–822} }
 @article{freedman_bowman_otvos_srinivasan_berenson_2000, title={Levels and correlates of LDL and VLDF, particle sizes among children: the Bogalusa heart study}, volume={152}, ISSN={["1879-1484"]}, DOI={10.1016/S0021-9150(99)00495-5}, abstractNote={Levels of lipids and lipoproteins among children vary by sex and race/ethnicity, and are correlated with age, obesity, and other characteristics. There is, however, little information on the distribution and correlates of low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) subclasses in early life. We used nuclear magnetic resonance (NMR) spectroscopy to determine mean LDL and VLDL particle sizes among 10- to 17-year-olds (n=918) who participated in the 1992-94 examination of the Bogalusa heart study. As compared with girls, boys had a smaller (0.1 nm) mean LDL particle size and a larger (0.9 nm) mean VLDL size; furthermore, the average size of VLDL particles increased with age among white boys but not among other children. Although there were also black/white differences in particle sizes, with black children having larger LDL and smaller VLDL particles, these racial contrasts could be attributed to differences in lipid levels. Levels of triglycerides, insulin, and relative weight were associated with the size of VLDL (positive) and LDL (negative) particles. These results suggest that the analysis of lipoprotein subclasses may provide a better understanding of the role of various risk factors in the development of coronary heart disease}, number={2}, journal={ATHEROSCLEROSIS}, author={Freedman, DS and Bowman, BA and Otvos, JD and Srinivasan, SR and Berenson, GS}, year={2000}, month={Oct}, pages={441–449} }
 @article{yu_ginsburg_ml o'toole_otvos_douglas_rifai_1999, title={Acute changes in serum lipids and lipoprotein subclasses in triathletes as assessed by proton nuclear magnetic resonance spectroscopy}, volume={19}, ISSN={["1524-4636"]}, DOI={10.1161/01.ATV.19.8.1945}, abstractNote={
            Abstract
            —Exercise is associated with changes in lipids that may protect against coronary heart disease (CHD). In this study of 28 triathletes, we analyzed acute changes in serum lipid and lipoprotein concentrations after completion of the 1995 World Championship Hawaii Ironman Triathlon. With standard laboratory assays, we demonstrate significant decreases in total cholesterol, VLDL cholesterol, ApoB100, and Lp(a). Total HDL cholesterol increased significantly immediately after the race. With a novel proton NMR spectroscopy assay, we demonstrate that smaller diameter LDL particles, corresponding to small, dense LDL, declined by 62%. Moreover, larger HDL subclasses, whose levels are inversely associated with CHD, increased significantly by 11%. Smaller HDL subclasses, which have been directly associated with CHD in some studies, acutely decreased by 16%. Therefore, exercise not only acutely induces changes in lipoprotein concentrations among the standard species in a manner that favorably affects CHD risk, but also induces favorable changes in specific lipoprotein subclass size distribution that also may alter CHD risk independently of the total lipoprotein serum concentration.
          }, number={8}, journal={ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY}, author={Yu, HH and Ginsburg, GS and ML O'Toole and Otvos, JD and Douglas, PS and Rifai, N}, year={1999}, month={Aug}, pages={1945–1949} }
 @article{couture_otvos_cupples_wilson_schaefer_ordovas_1999, title={Association of the A-204C polymorphism in the cholesterol 7 alpha-hydroxylase gene with variations in plasma low density lipoprotein cholesterol levels in the Framingham Offspring Study}, volume={40}, number={10}, journal={Journal of Lipid Research}, author={Couture, P. and Otvos, J. D. and Cupples, L. A. and Wilson, P. W. F. and Schaefer, E. J. and Ordovas, J. M.}, year={1999}, pages={1883–1889} }
 @article{grundy_vega_otvos_rainwater_cohen_1999, title={Hepatic lipase activity influences high density lipoprotein subclass distribution in normotriglyceridemic men: genetic and pharmacological evidence}, volume={40}, number={2}, journal={Journal of Lipid Research}, author={Grundy, S. M. and Vega, G. L. and Otvos, J. D. and Rainwater, D. L. and Cohen, J. C.}, year={1999}, pages={229–234} }
 @article{otvos_1999, title={Measurement of triglyceride-rich lipoproteins by nuclear magnetic resonance spectroscopy}, volume={22}, DOI={10.1002/clc.4960221405}, abstractNote={Nuclear magnetic resonance (NMR) spectroscopy is being used to determine the concentrations of very low‐density lipoprotein (VLDL), low‐density lipoprotein (LDL), and high‐density lipoprotein (HDL) subclasses of different size. These subclasses have unequal associations with coronary heart disease. Nuclear magnetic resonance distinguishes among the subclasses on the basis of slight differences in the spectral properties of the lipids carried within the particles, which vary according to the diameter of the phospholipid shell. Studies using NMR spectroscopy have shown that individuals with elevated triglycerides are likely to have higher‐risk lipoprotein subclass profiles. Triglyceride‐rich lipoproteins drive the metabolic reactions that produce LDL of abnormal size and cholesterol content. The quantities of these abnormal LDL particles and the associated risk of coronary heart disease are underestimated by conventional cholesterol measurements. Nuclear magnetic resonance spectroscopy measures lipoprotein subclasses directly and efficiently, and produces information that may improve the assessment and management of cardiovascular disease risk.}, number={6 Suppl.}, journal={Clinical Cardiology (Los Altos, Calif.)}, author={Otvos, J.}, year={1999}, pages={II 21–27} }
 @article{zangger_oz_otvos_armitage_1999, title={Three-dimensional solution structure of mouse [Cd-7]-metallothionein-1 by homonuclear and heteronuclear NMR spectroscopy}, volume={8}, ISSN={["1469-896X"]}, DOI={10.1110/ps.8.12.2630}, abstractNote={Abstract}, number={12}, journal={PROTEIN SCIENCE}, author={Zangger, K and Oz, G and Otvos, JD and Armitage, IM}, year={1999}, month={Dec}, pages={2630–2638} }
 @article{li_otvos_1998, title={Biphasic kinetics of Zn2+ removal from Zn metallothionein by nitrilotriacetate are associated with differential reactivity of the two metal clusters}, volume={70}, ISSN={["1873-3344"]}, DOI={10.1016/S0162-0134(98)10013-2}, abstractNote={We investigated the kinetics of nitrilotriacetate (NTA) extraction of Zn2+ from Zn7-metallothionein (MT) and a metal-hybrid derivative, Zn4Ag6MT, in which the Zn2+ and Ag+ ions occupy sites in the C-terminal α and N-terminal β domains of the protein, respectively. Biphasic kinetics were observed for Zn7MT under pseudo-first-order conditions. Rate constants were (5.2±0.6)×10−3 and (1.0±0.3)×10−4s−1 in 20 mM phosphate, 100 mM KF, pH 7.5 at 23∘C. In contrast, Zn4Ag6MT showed a single kinetic step with a rate constant of (2.9±0.4)×10−3s−1. These results indicate that the biphasic reactivity of Zn7MT stems from differential susceptibility of the metal in the two metal–thiolate clusters to removal by competing ligands, with Zn2+ in the more stable α-domain cluster reacting faster than that in the less stable β-domain cluster. Such behavior suggests that the structures of the two domains of mammalian MT may have evolved to assure that Cu binding does not compromise the structural characteristics that allow Zn to be rapidly transferred from MT to essential cellular ligands.}, number={3-4}, journal={JOURNAL OF INORGANIC BIOCHEMISTRY}, author={Li, H and Otvos, JD}, year={1998}, month={Jul}, pages={187–194} }
 @article{vadlamudi_maclean_israel_marks_hickey_otvos_barakat_1998, title={Effects of oral combined hormone replacement therapy on plasma lipids and lipoproteins}, volume={47}, ISSN={["1532-8600"]}, DOI={10.1016/S0026-0495(98)90327-4}, abstractNote={Hormone replacement therapy has been shown to decrease the risk of coronary heart disease (CHD) in menopausal women. In this cross-sectional study, we addressed the following question: What effects would combined oral hormone replacement therapy have on plasma lipid and lipoprotein profiles independent of the other known CHD risk factors? We analyzed the plasma lipoproteins of two groups of menopausal women who were randomly selected from a large database of individuals. One group (n = 10) was not taking any hormone replacement therapy (NO HRT), while the second group (n = 8) was taking a daily dose of 0.625 mg conjugated estrogen and 2.5 mg medroxyprogesterone orally (PremPro, Wyeth-Ayerst, Philadelphia, PA) for at least 6 months (HRT). The two groups were not different in age, body weight, percent body fat, body mass index (BMI), waist to hip ratio, blood pressure, or insulin and glucose levels. High-density lipoprotein (HDL)-cholesterol was significantly higher (P < .05) in the HRT group. The total cholesterol (TC) to HDL-cholesterol ratio was significantly lower for HRT versus NO HRT (P < .05). Apolipoprotein (apo) A-1, the apo A-1/B ratio, and lecithin:cholesterol acyltransferase (LCAT) activity were significantly higher in HRT (P < .05). Lipoprotein subclass profiles measured by nuclear magnetic resonance (NMR) spectroscopy showed an increase in larger HDL subpopulations (H3 and H4) in HRT (P < .05), which are considered antiatherogenic. No differences were seen in the cholesterol concentration or size of low-density lipoprotein (LDL) subpopulations in HRT compared with NO HRT. These results indicate that the combined estrogen and progesterone treatment leads to beneficial effects on plasma lipoproteins. The beneficial effects include (1) increases in HDL-cholesterol and predominance of HDL2, (2) no adverse effects on LDL subpopulation distribution, and (3) increases in apo A-1 levels and LCAT activity, which indicate an improvement in reverse cholesterol transport.}, number={10}, journal={METABOLISM-CLINICAL AND EXPERIMENTAL}, author={Vadlamudi, S and Maclean, P and Israel, RG and Marks, RH and Hickey, M and Otvos, J and Barakat, H}, year={1998}, month={Oct}, pages={1222–1226} }
 @article{lilley_spivey_vadlamudi_otvos_cummings_barakat_1998, title={Lipid and lipoprotein responses to oral combined hormonereplacement therapy in normolipemic obese women with controlledtype 2 diabetes mellitus}, volume={38}, number={12}, journal={Journal of Clinical Pharmacology}, author={Lilley, S. H. and Spivey, J. M. and Vadlamudi, S. and Otvos, J. and Cummings, D. M. and Barakat, H.}, year={1998}, pages={1107–1115} }
 @article{giri_thompson_taxel_contois_otvos_allen_ens_wu_waters_1998, title={Oral estrogen improves serum lipids, homocysteine and fibrinolysis in elderly men}, volume={137}, ISSN={["1879-1484"]}, DOI={10.1016/S0021-9150(98)00022-7}, abstractNote={The effects of estrogen on cardiovascular risk factors have been less well defined in men than in women. We measured lipid and lipoprotein concentrations, lipoprotein particle size distributions, lipoprotein (a), homocysteine, and markers of thrombosis and fibrinolysis in 22 healthy elderly men (age 74±3 years, mean±S.D.) before and after 9 weeks of treatment with 0.5, 1 or 2 mg/day of oral micronized 17β-estradiol. LDL-C (−6%), apo B (−9%), triglyceride (−5%), and homocysteine (−11%) concentrations decreased with estradiol, whereas HDL-C (+14%) increased. Intermediate-size VLDL subclass concentrations were lowered and LDL and HDL subclass levels altered in such a way as to cause average LDL and HDL particle size to increase. Lipoprotein (a) did not change. Fibrinogen (−13%) and plasminogen activator inhibitor-1 (PAI-1) concentrations (−26%) decreased, but there were no changes in thrombotic markers including thrombin-antithrombin III complex, prothrombin fragment 1.2, D-dimer, antithrombin activity, protein-C and S and von Willebrand factor antigen. Breast tenderness occurred in four men and heartburn in five but did not require discontinuation of treatment. We conclude that oral estrogen in men reduces homocysteine, fibrinogen, and PAI-1 concentrations and favorably influences VLDL, LDL and HDL subclass levels without increasing markers of thrombotic risk.}, number={2}, journal={ATHEROSCLEROSIS}, author={Giri, S and Thompson, PD and Taxel, P and Contois, JH and Otvos, J and Allen, R and Ens, G and Wu, AHB and Waters, DD}, year={1998}, month={Apr}, pages={359–366} }
 @article{giri_thompson_taxel_contois_otvos_allen_ens_wu_waters_1998, title={Oral estrogen improves serum lipids, homocysteine and fibrinolysis in elderly men (vol. 137, pg. 359, 1998)}, volume={138}, number={2}, journal={Atherosclerosis}, author={Giri, S. and Thompson, P. D. and Taxel, P. and Contois, J. H. and Otvos, J. and Allen, R. and Ens, G. and Wu, A. H. B. and Waters, D. D.}, year={1998}, pages={403} }
 @article{freedman_otvos_jeyarajah_barboriak_anderson_walker_1998, title={Relation of lipoprotein subclasses as measured by proton nuclear magnetic resonance spectroscopy to coronary artery disease}, volume={18}, ISSN={["1524-4636"]}, DOI={10.1161/01.ATV.18.7.1046}, abstractNote={
            Abstract
            —Although each of the major lipoprotein fractions is composed of various subclasses that may differ in atherogenicity, the importance of this heterogeneity has been difficult to ascertain owing to the labor-intensive nature of subclass measurement methods. We have recently developed a procedure, using proton nuclear magnetic resonance (NMR) spectroscopy, to simultaneously quantify levels of subclasses of very low density (VLDL), low density (LDL), and high density (HDL) lipoproteins; subclass distributions determined with this method agree well with those derived by gradient gel electrophoresis. The objective of the current study of 158 men was to examine whether NMR-derived lipoprotein subclass levels improve the prediction of arteriographically documented coronary artery disease (CAD) when levels of lipids and lipoproteins are known. We found that a global measure of CAD severity was positively associated with levels of large VLDL and small HDL particles and inversely associated with intermediate size HDL particles; these associations were independent of age and standard lipid measurements. At comparable lipid and lipoprotein levels, for example, men with relatively high (higher than the median) levels of either small HDL or large VLDL particles were three to four times more likely to have extensive CAD than were the other men; the 27 men with high levels of both large VLDL and small HDL were 15 times more likely to have extensive CAD than were men with low levels. In contrast, adjustment for levels of triglycerides or HDL cholesterol greatly reduced the relation of small LDL particles to CAD. These findings suggest that large VLDL and small HDL particles may play important roles in the development of occlusive disease and that their measurement, which is not possible with routine lipid testing, may lead to more accurate risk assessment.
          }, number={7}, journal={ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY}, author={Freedman, DS and Otvos, JD and Jeyarajah, EJ and Barboriak, JJ and Anderson, AJ and Walker, JA}, year={1998}, month={Jul}, pages={1046–1053} }
 @article{parsons_skapek_neufeld_kuhlman_young_donnelly_brunzell_otvos_sallan_rifai_1997, title={Asparaginase associated lipid abnormalities in children with acute lymphoblastic leukemia}, volume={89}, number={6}, journal={Blood}, author={Parsons, S. K. and Skapek, S. X. and Neufeld, E. J. and Kuhlman, C. and Young, M. L. and Donnelly, M. and Brunzell, J. D. and Otvos, James D. and Sallan, S. E. and Rifai, N.}, year={1997}, pages={1886–1895} }
 @misc{otvos_1994, title={Method and apparatus for measuring classes and subclasses of lipoproteins}, volume={5,343,389}, number={1994 Aug. 30}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Otvos, J.}, year={1994} }