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Articles by James D. Otvos
Total Records ( 5 ) for James D. Otvos
  Wm. James Howard , Marie Russell , Jerome L. Fleg , Mihriye Mete , Tauqeer Ali , Richard B. Devereux , James M. Galloway , James D. Otvos , Robert E. Ratner , Mary J. Roman , Angela Silverman , Jason G. Umans , Neil J. Weissman , Charlton Wilson and Barbara V. Howard
 

Background

Lowering low-density lipoprotein cholesterol (LDL-C) with statins reduces atherosclerosis. LDL and high-density lipoprotein (HDL) are commonly measured by their cholesterol content, but non-HDL cholesterol, LDL particle number (LDL-P), or total apolipoprotein B (apoB) may be better predictors of cardiovascular risk. Few studies have examined the relationship among lipoprotein levels and composition before and after interventions to lower LDL-C and non-HDL-C.

Objective

We sought to measure changes in carotid artery intimal media thickness (CIMT) and lipid concentration and composition during 36 months of statin therapy.

Methods

Analyses were conducted on 418 diabetic individuals, with complete data and no previous cardiovascular events, who were randomized to aggressive (AG) versus standard treatment for LDL-C, non-HDL-C, and systolic blood pressure as part of the Stop Atherosclerosis in Native Diabetics Study (SANDS).

Results

The AG group achieved average LDL-C and non-HDL-C of 71 mg/dL and 100 mg/dL and a decrease in CIMT. No significant interactions were observed between treatment effect and initial levels of LDL-C, non-HDL-C, HDL-C, triglycerides, apoB, or LDL-P. Decreases in LDL-C (P < .005) and non-HDL-C (P < .001) were independently correlated with CIMT regression in the AG group. Changes in apoB and LDL-P demonstrated borderline correlations with CIMT regression (P=.07 and P=.09).

Conclusions

In diabetic adults with no previous cardiovascular events, treatment to current targets for lipids and systolic blood pressure reduces atherosclerosis progression and when more aggressive targets are met, atherosclerosis regresses. The aggressive targets for LDL-C and non-HDL-C appeared to be the main determinants of CIMT regression and were more predictive of this outcome than changes in LDL-P or apoB.

  James D. Otvos , Samia Mora , Irina Shalaurova , Philip Greenland , Rachel H. Mackey and David C. Goff Jr.
 

Background

The amount of cholesterol per low-density lipoprotein (LDL) particle is variable and related in part to particle size, with smaller particles carrying less cholesterol. This variability causes concentrations of LDL cholesterol (LDL-C) and LDL particles (LDL-P) to be discordant in many individuals.

Methods

LDL-P measured by nuclear magnetic resonance spectroscopy, calculated LDL-C, and carotid intima-media thickness (IMT) were assessed at baseline in the Multi-Ethnic Study of Atherosclerosis, a community-based cohort of 6814 persons free of clinical cardiovascular disease (CVD) at entry and followed for CVD events (n = 319 during 5.5-year follow-up). Discordance, defined as values of LDL-P and LDL-C differing by ≥12 percentile units to give equal-sized concordant and discordant subgroups, was related to CVD events and to carotid IMT in models predicting outcomes for a 1 SD difference in LDL-C or LDL-P, adjusted for age, gender, and race.

Results

LDL-C and LDL-P were associated with incident CVD overall: hazard ratios (HR 1.20, 95% CI [CI] 1.08−1.34; and 1.32, 95% CI 1.19−1.47, respectively, but for those with discordant levels, only LDL-P was associated with incident CVD (HR 1.45, 95% CI 1.19−1.78; LDL-C HR 1.07, 95% CI 0.88−1.30). IMT also tracked with LDL-P rather than LDL-C, ie, adjusted mean IMT of 958, 932, and 917 μm in the LDL-P > LDL-C discordant, concordant, and LDL-P < LDL-C discordant subgroups, respectively, with the difference persisting after adjustment for LDL-C (P = .002) but not LDL-P (P = .60).

Conclusions

For individuals with discordant LDL-C and LDL-P levels, the LDL-attributable atherosclerotic risk is better indicated by LDL-P.

  James D. Otvos
  Not available
  Harold E. Bays , Rene A. Braeckman , Christie M. Ballantyne , John J. Kastelein , James D. Otvos , William G. Stirtan and Paresh N. Soni
 

Background

Icosapent ethyl (IPE; formerly AMR101) is a high-purity prescription form of eicosapentaenoic acid ethyl ester. In the MARINE study we evaluated the efficacy and safety of IPE in patients with very high triglycerides (TG; ≥500 mg/dL) and previously demonstrated significant reductions in TG levels with no significant increases in low-density lipoprotein (LDL) cholesterol levels.

Objectives

In this follow-up, exploratory analysis, we report the effects of IPE on lipoprotein particle concentration and size.

Methods

MARINE was a phase 3, multicenter, placebo-controlled, randomized, double-blind, 12-week study. Hypertriglyceridemic patients (N = 229) were randomized to three treatment groups: IPE 4 g/day, IPE 2 g/day, or placebo. Lipoprotein particle concentrations and sizes were measured by nuclear magnetic resonance spectroscopy.

Results

Compared with placebo, IPE 4 g/day significantly reduced median concentrations of large very-low-density lipoprotein (VLDL; −27.9%; P = .0211), total LDL (−16.3%; P = .0006), small LDL (−25.6%; P < .0001), and total high-density lipoprotein (HDL; −7.4%; P = .0063) particles and reduced VLDL particle size (−8.6%; P = .0017). In this patient population with TG ≥500 mg/dL, IPE did not significantly change the overall sizes of LDL or HDL particles.

Conclusion

IPE 4 g/day significantly reduced large VLDL, total LDL, small LDL, and total HDL particle concentrations and VLDL particle size in patients with TG ≥500 mg/dL. Changes in VLDL particle concentration and size reflect the TG-lowering effects of eicosapentaenoic acid. The reduction in LDL particle concentration with IPE is novel among ω-3 therapies and is consistent with the previously reported reduction in apolipoprotein B and lack of LDL-C increase with IPE in patients with very high TG levels.

  Peter O. Kwiterovich , Donna G. Virgil , Audrey Y. Chu , Victor A. Khouzami , Petar Alaupovic and James D. Otvos
 

Background

Lipoprotein subfractions in infants may predict the risk of cardiovascular disease factors in children.

Objective

To examine the relationships between lipid and nonlipid factors and lipoprotein subfractions in infants at birth and follow-up (FU) and in their parents.

Methods

Prospective study in a community-based hospital of 103 families ascertained through a pregnant mother at 36 weeks gestation or older. Of 103 infants studied at birth, 85 were sampled at FU at 2-3 months of age, along with 76 fathers. Lipids, lipoproteins, and their subclasses were determined by nuclear magnetic resonance spectroscopy. Correlations of lipid-related parameters were calculated using Spearman rank correlations.

Results

Female gender in infants and use of formula only were the only nonlipid variables associated with lipoprotein subfractions. LDL parameters were significantly correlated between infants at birth and FU. The largest high-density lipoprotein subfraction, H5C, was the only lipid variable significantly associated between mothers and infants at birth. Paternal low-density lipoprotein size was significantly correlated with that of infants at FU but not at birth. In each of the four groups, markedly inverse interrelationships were found between H5C and small LDL particles. At birth and at FU, apoC-I was strongly related with H5C but not TG. Conversely, apoC-I in the parents was strongly related with TG but not H5C.

Conclusion

Significant relationships were found between lipoprotein subfractions within infants at birth and FU and their parents. ApoC-I and H5C levels very early in life may affect the development of dyslipidemia and obesity in childhood.

 
 
 
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