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Lipoprotein particle subclasses, cardiovascular disease and HIV infection.

ABSTRACT: To study the association of lipoprotein particles with CVD in a subgroup of HIV-infected patients who were enrolled in the Strategies for Management of Anti-Retroviral Therapy (SMART) study. SMART was a trial of intermittent use of ART (drug conservation [DC]) versus continuous of ART (viral suppression [VS]).In a nested case-control study, lipoprotein particles (p) by nuclear magnetic resonance were measured at baseline and at the visit prior to the CVD event (latest levels) for 248 patients who had a CVD event and for 480 matched controls. Odds ratios (ORs) were estimated using conditional logistic models.Total, large and small HDL-p, but not VLDL-p nor LDL-p, were significantly and inversely associated with CVD and its major component, non-fatal coronary heart disease. The HDL-p associations with CVD were reduced after adjustment for high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6) and D-dimer. Latest levels of total HDL-p were also significantly inversely associated with CVD; treatment interruption led to decrease of total HDL-p; adjusting for latest HDL-p did not explain the greater risk of CVD that was observed in the DC versus VS group.Lipoprotein particles, especially lower levels of small and large HDL-p identify HIV-infected patients at increased risk of CVD independent of other CVD risk factors.

SUBMITTER: Duprez DA

PROVIDER: S-EPMC2818719 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Lipoprotein particle subclasses, cardiovascular disease and HIV infection.

Duprez Daniel A DA Kuller Lewis H LH Tracy Russell R Otvos James J Cooper David A DA Hoy Jennifer J Neuhaus Jacqueline J Paton Nicholas I NI Friis-Moller Nina N Lampe Fiona F Liappis Angelike P AP Neaton James D JD

Atherosclerosis 20090513 2

<h4>Objective</h4>To study the association of lipoprotein particles with CVD in a subgroup of HIV-infected patients who were enrolled in the Strategies for Management of Anti-Retroviral Therapy (SMART) study. SMART was a trial of intermittent use of ART (drug conservation [DC]) versus continuous of ART (viral suppression [VS]).<h4>Methods</h4>In a nested case-control study, lipoprotein particles (p) by nuclear magnetic resonance were measured at baseline and at the visit prior to the CVD event ( ...[more]

PMID: 19515371

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Project description:BackgroundNuclear magnetic resonance (NMR) spectroscopy measures the number and size of lipoprotein particles instead of their cholesterol or triglyceride content, but its clinical utility is uncertain.Methods and resultsBaseline lipoproteins were measured by NMR in 27 673 initially healthy women followed up for incident cardiovascular disease (n=1015) over an 11-year period. After adjustment for nonlipid risk factors, hazard ratios and 95% confidence intervals for the top versus the bottom quintile of NMR-measured lipoprotein particle concentration (measured in particles per liter) were 2.51 (1.91 to 3.30) for low-density lipoprotein (LDL(NMR)), 0.91 (0.75 to 1.12) for high-density lipoprotein (HDL(NMR)), 1.71 (1.38 to 2.12) for very low-density lipoprotein (VLDL(NMR)), and 2.25 (1.80 to 2.81) for the LDL(NMR)/HDL(NMR) ratio. Similarly adjusted results for NMR-measured lipoprotein particle size (measured in nanometers) were 0.64 (0.52 to 0.79) for LDL(NMR) size, 0.65 (0.51 to 0.81) for HDL(NMR) size, and 1.37 (1.10 to 1.70) for VLDL(NMR) size. Hazard ratios for NMR measures were comparable but not superior to standard lipids (total cholesterol 2.08 [1.63 to 2.67], LDL cholesterol 1.74 [1.40 to 2.16], HDL cholesterol 0.52 [0.42 to 0.64], triglycerides 2.58 [1.95 to 3.41], non-HDL cholesterol 2.52 [1.95 to 3.25], total/HDL cholesterol ratio 2.82 [2.23 to 3.58]) and apolipoproteins (B(100) 2.57 [1.98 to 3.33], A-1 0.63 [0.52 to 0.77], and B(100)/A-1 ratio 2.79 [2.21 to 3.54]). Essentially no reclassification improvement was found with the addition of the LDL(NMR) particle concentration or apolipoprotein B(100) to a model that already included the total/HDL cholesterol ratio and nonlipid risk factors (net reclassification index 0% and 1.9%, respectively), nor did the addition of either variable result in a statistically significant improvement in the c-index.ConclusionsIn this prospective study of healthy women, cardiovascular disease risk prediction associated with lipoprotein profiles evaluated by NMR was comparable but not superior to that of standard lipids or apolipoproteins.

Project description:BACKGROUND:Despite strong and consistent prospective associations of elevated low-density lipoprotein (LDL) cholesterol concentration with incident coronary and cerebrovascular disease, data for incident peripheral artery disease (PAD) are less robust. Atherogenic dyslipidemia characterized by increased small LDL particle (LDL-P) concentration, rather than total LDL cholesterol content, along with elevated triglyceride-rich lipoproteins and low high-density lipoprotein (HDL) cholesterol (HDL-C), may be the primary lipid driver of PAD risk. METHODS:The study population was a prospective cohort study of 27 888 women ?45 years old free of cardiovascular disease at baseline and followed for a median of 15.1 years. We tested whether standard lipid concentrations, as well as nuclear magnetic resonance spectroscopy-derived lipoprotein measures, were associated with incident symptomatic PAD (n=110) defined as claudication and/or revascularization. RESULTS:In age-adjusted analyses, while LDL cholesterol was not associated with incident PAD, we found significant associations for increased total and small LDL-P concentrations, triglycerides, and concentrations of very LDL (VLDL) particle (VLDL-P) subclasses, increased total cholesterol (TC):HDL-C, low HDL-C, and low HDL particle (HDL-P) concentration (all P for extreme tertile comparisons <0.05). Findings persisted in multivariable-adjusted models comparing extreme tertiles for elevated total LDL-P (adjusted hazard ratio [HRadj] 2.03; 95% CI, 1.14-3.59), small LDL-P (HRadj 2.17; 95% CI, 1.10-4.27), very large VLDL-P (HRadj 1.68; 95% CI, 1.06-2.66), medium VLDL-P (HRadj 1.98; 95% CI, 1.15-3.41), and TC:HDL-C (HRadj, 3.11; 95% CI, 1.67-5.81). HDL was inversely associated with risk; HRadj for extreme tertiles of HDL-C and HDL-P concentration were 0.30 ( P trend < 0.0001) and 0.29 ( P trend < 0.0001), respectively. These components of atherogenic dyslipidemia, including small LDL-P, medium and very large VLDL-P, TC:HDL-C, HDL-C, and HDL-P, were more strongly associated with incident PAD than incident coronary and cerebrovascular disease. Finally, the addition of LDL-P and HDL-P concentration to TC:HDL-C measures identified women at heightened PAD risk. CONCLUSIONS:In this prospective study, nuclear magnetic resonance-derived measures of LDL-P, but not LDL cholesterol, were associated with incident PAD. Other features of atherogenic dyslipidemia, including elevations in TC:HDL-C, elevations in triglyceride-rich lipoproteins, and low standard and nuclear magnetic resonance-derived measures of HDL, were significant risk determinants. These data help clarify prior inconsistencies and may elucidate a unique lipoprotein signature for PAD compared to coronary and cerebrovascular disease. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov/ . Unique Identifier: NCT00000479.

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Lipoprotein particle subclasses, cardiovascular disease and HIV infection.

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Lipoprotein particle subclasses, cardiovascular disease and HIV infection.

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