The Impact of Climate Change on the Food System in Toronto.

As part of its Climate Change and Health Strategy, in 2017, Toronto Public Health engaged stakeholders from across the food system to complete a high-level vulnerability assessment of the impact of climate change on the food system in Toronto. Using the Ontario Climate Change and Health Vulnerability and Adaptation Assessment Guidelines, the City of Toronto's High-Level Risk Assessment Tool, and a strategic framework developed by the Initiative for a Competitive Inner City, Toronto Public Health identified the most significant extreme weather event risks to food processing, distribution and access in Toronto. Risks associated with three extreme weather events that are the most likely to occur in Toronto due to climate change were analyzed: significant rain and flooding, an extended heat wave, and a major winter ice storm. The analysis finds that while extreme weather events could potentially disrupt Toronto's food supply, the current risk of an extended, widespread food supply disruption is relatively low. However, the findings highlight that a concerted effort across the food system, including electrical and fuel providers, is needed to address other key vulnerabilities that could impact food access, especially for vulnerable populations. Interruptions to electricity will have food access and food safety impacts, while interruptions to the transportation network and fuel will have food distribution and access impacts. Actions to mitigate these risks could include addressing food access vulnerabilities through ongoing city-wide strategies and integrating food access into the City's emergency response planning. The next steps will include engaging with multiple partners across the city to understand and strengthen the "last mile" of food distribution and develop community food resilience action plans for vulnerable neighbourhoods.

A combined emission and receptor-based approach to modelling environmental noise in urban environments.

The state of practice for noise assessment utilizes established standards for emission and propagation modelling of linear and point sources. Recently, land use regression (LUR) modelling has emerged as an alternative method due to relatively low data and computing resource demands. However, a limitation of LUR modelling is that is does not account for noise attenuation and reflections by features of the built environment. This study demonstrates and validates a method that combines the two modelling frameworks to exploit their respective strengths: Emission and propagation based prediction of traffic noise, the predominant source of noise at the level of streetscapes, and a LUR-based correction for noise sources that vary on spatial scales beyond the streetscape. Multi-criteria analysis, location-allocation modelling and stakeholder consultation identified 220 monitoring sites with optimal coverage for a 1-week sampling period. A subset of sites was used to validate a road traffic noise emission and propagation model and to specify a LUR model that predicted the contribution of other sources. The equivalent 24-h sound pressure level (LAeq) for all sites was 62.9 dBA (SD 6.4). This varied by time of day, weekday, types of roads and land uses. The traffic noise emission model demonstrated a high level of covariance with observed noise levels, with R2 values of 0.58, 0.60 and 0.59 for daytime, nighttime and 24-h periods, respectively. Combined with LUR models to correct for other noise sources, the hybrid models R2 values were 0.64, 0.71 and 0.67 for the respective time periods. The study showed that road traffic noise emissions account for most of the variability of total environmental noise in Toronto. The combined approach to predict fine resolution noise exposures with emission and receptor-based models presents an effective alternative to noise modelling approaches based on emission and propagation or LUR modelling.

Development of a guide to applying precaution in local public health.

PURPOSE: The precautionary principle (PP) urges actions to prevent harm even in the face of scientific uncertainty. Members of Toronto Public Health (TPH) sought guidance on applying precaution. METHODS: We searched five bibliographic databases (yield 60 articles from 1996 to 2009 and 8 from 2009 to 2011) and Google (yield 11 gray literature sources) for material relevant to local public health. From these sources, we extracted questions until saturation was reached (n =55). We applied these questions retrospectively to eight case studies where TPH felt precaution was applied. We ranked questions for their importance in applying precaution. RESULTS: Our final guide included 35 questions in five domains: context, assessment, alternative interventions, implementation, and monitoring and evaluation. Importance rankings varied across cases, but the role of stakeholders in driving precautionary action was consistent. Monitoring and evaluation components could have been strengthened across cases. CONCLUSION: The TPH guide can assist municipal environmental health practitioners in applying precaution in a more transparent manner.

Healthy Toronto by Design: Promoting a healthier built environment.

Chronic diseases, obesity and sedentary lifestyles are some of the health challenges facing Canada today. There is increasing recognition and evidence that the way our cities are planned, designed and built can contribute to these problems. Many of the policy levers to address the built environment exist outside the health sector and at the municipal level in areas such as urban planning, transportation, parks and recreation, and housing. The challenge for the public health sector is to build and sustain partnerships and collaboration across various sectors to ensure that health is considered in built environment policies. As the public health unit for the city of Toronto and part of the municipal government, Toronto Public Health is in a unique position to provide leadership, advocacy and support for healthy municipal public policies related to the built environment. This article provides some examples of CLASP (Coalitions Linking Action and Science for Prevention) initiatives undertaken to help create support for healthy public policies in the built environment and suggests that the "Healthy Cities" approach is a useful framework to promote policy change in the built environment at the municipal level.

Novel lipoprotein density profiling in healthy dogs of various breeds, healthy Miniature Schnauzers, and Miniature Schnauzers with hyperlipidemia.

BACKGROUND: Despite the importance of abnormalities in lipoprotein metabolism in clinical canine medicine, the fact that most previously used methods for lipoprotein profiling are rather laborious and time-consuming has been a major obstacle to the wide clinical application and use of lipoprotein profiling in this species. The aim of the present study was to assess the feasibility of a continuous lipoprotein density profile (CLPDP) generated within a bismuth sodium ethylenediaminetetraacetic acid (NaBiEDTA) density gradient to characterize and compare the lipoprotein profiles of healthy dogs of various breeds, healthy Miniature Schnauzers, and Miniature Schnauzers with primary hypertriacylglycerolemia. A total of 35 healthy dogs of various breeds with serum triacylglycerol (TAG) and cholesterol concentrations within their respective reference intervals were selected for use as a reference population. Thirty-one Miniature Schnauzers with serum TAG and cholesterol concentrations within their respective reference intervals and 31 Miniature Schnauzers with hypertriacylglyceridemia were also included in the study. RESULTS: The results suggest that CLPDP using NaBiEDTA provides unique diagnostic information in addition to measurements of serum TAG and cholesterol concentrations and that it is a useful screening method for dogs with suspected lipoprotein metabolism disorders. Using the detailed and continuous density distribution information provided by the CLPDP, important differences in lipoprotein profiles can be detected even among dogs that have serum TAG and cholesterol concentrations within the reference interval. Miniature Schnauzers with serum TAG and cholesterol concentrations within the reference interval had significantly different lipoprotein profiles than dogs of various other breeds. In addition, it was further established that specific lipoprotein fractions are associated with hypertriacylglyceridemia in Miniature Schnauzers. CONCLUSIONS: The results of the present study suggest that density gradient ultracentrifugation using NaBiEDTA is a useful screening method for the study of lipoprotein profiles in dogs. Therefore, this method could potentially be used for diagnostic purposes for the separation of dogs suspected of having lipoprotein abnormalities from healthy dogs.

Mobilization of ectopic yolk in Gallus gallus domesticus: a novel reverse lipid transport process.

In many oviparous animals, bursting type atresia of ovarian follicles occurs during the reproductive cycle, resulting in the escape of yolk into the extracellular compartment. In birds, this ectopic yolk is rapidly cleared by an unknown process that involves the appearance of yolk-engorged macrophage-like cells. To study this unique type of lipid transport, we injected young male chickens intra-abdominally with egg yolk. Absorption of egg yolk from the body cavity markedly increased the triacylglyceride-rich fraction (TRL) of plasma lipoproteins and was coincident with increased levels of plasma triacylglycerides (TAGs) but not non-esterified fatty acids (NEFAs). Thus, the transport of yolk lipids from the abdominal cavity appears to occur in lipoproteins and be more similar to the transport of hepatic TAGs to the periphery via lipoproteins than to transport of adipose TAGs to the periphery via NEFAs released by the action of lipases. When macrophages were exposed to yolk in vitro, they quickly phagocytized yolk; however, it is unclear whether this level of phagocytosis contributes significantly to total yolk clearance. Instead, the chicken macrophage may function more as a facilitator of yolk clearance through the modification of yolk lipoproteins and the regulation of the local and systemic immune response to ectopic yolk. Yolk appears to be anti-inflammatory in nature. Yolk did not increase levels of the inflammatory cytokines IL-1, IL-6 and IFNγ either in vivo or in vitro; in fact, yolk dampened many inflammatory changes caused by lipopolysaccharide (LPS). Conversely, LPS-induced inflammation retarded yolk clearance from the abdominal cavity and plasma TAG levels.

Human HDL containing a novel apoC-I isoform induces smooth muscle cell apoptosis.

AIMS: We discovered that some adults with coronary heart disease (CHD) have a high density lipoprotein (HDL) subclass which induces human aortic smooth muscle cell (ASMC) apoptosis in vitro. The purpose of this investigation was to determine what properties differentiate apoptotic and non-apoptotic HDL subclasses in adults with and without CHD. METHODS AND RESULTS: Density gradient ultracentrifugation was used to measure the particle density distribution and to isolate two HDL subclass fractions, HDL2 and HDL3, from 21 individuals, including 12 without CHD. The HDL fractions were incubated with ASMCs for 24 h; apoptosis was quantitated relative to C2-ceramide and tumour necrosis factor-alpha (TNF-α). The observed effect of some HDL subclasses on apoptosis was ∼6-fold greater than TNF-α and ∼16-fold greater than the cell medium. We observed that apoptotic HDL was (i) predominately associated with the HDL2 subclass; (ii) almost exclusively found in individuals with a higher apoC-I serum level and a novel, higher molecular weight isoform of apoC-I; and (iii) more common in adults with CHD, the majority of whom had high (>60 mg/dL) HDL-C levels. CONCLUSIONS: Some HDL subclasses enriched in a novel isoform of apoC-I induce extensive ASMC apoptosis in vitro. Individuals with this apoptotic HDL phenotype generally have higher apoC-I and HDL-C levels consistent with an inhibitory effect of apoC-I on cholesteryl ester transfer protein activity. The association of this phenotype with processes that can promote plaque rupture may explain a source of CHD risk not accounted for by the classical risk factors.

Developing high performance lipoprotein density profiling for use in clinical studies relating to cardiovascular disease.

Early detection of the beginning stage of cardiovascular disease (CVD) is an approach to prevention because the process is reversible at this stage. Consequently, several methods for screening for CVD have been introduced in recent years incorporating different analytical methods for characterizing the population of blood-borne lipoprotein subclasses. The gold standard method for lipoprotein subclassification is based on lipoprotein density measured by sedimentation equilibrium using the ultracentrifuge. However, this method has not been adopted for clinical studies because of difficulties in achieving the precision required for distinguishing individuals with and without CVD particularly when statistical classification methods are used. The objective of this study was to identify and improve the major factors that influence the precision of measurement of lipoprotein density profile by sedimentation equilibrium analysis and labeling with a fluorescent probe. The study has two phases, each contributing to precision. The first phase focuses on the ultracentrifugation-related variables, and the second phase addresses those factors involved in converting the fluorescent lipoprotein density profile to a digital format compatible with statistical analysis. The overall improvement in precision was on the order of a factor of 5, sufficient to be effectively applied to ongoing classification studies relating to CVD risk assessment.

Isoforms of apolipoprotein C-I associated with individuals with coronary artery disease.

Apolipoprotein C-I (apoC-I) is a 6.6kDa serum protein associated with high density lipoproteins (HDL) and triglyceride-rich lipoproteins. In this study, apoC-I was examined in high density lipoprotein subfractions from individuals with and without coronary artery disease (CAD). New isoforms of apoC-I, were detected in the cohort of individuals with CAD using mass spectrometry while the expected apoC-I isoforms were absent. In addition, the apoC-I mass spectra for the CAD cohort had satellite peaks indicative of the involvement of oxidative processes. Further analysis of the mass spectra of the CAD and non-CAD cohorts suggest that the origin of these new isoforms may be due to genetic mutations that could compromise the function of apoC-I.

Effect of sterol carrier protein-2 gene ablation on HDL-mediated cholesterol efflux from cultured primary mouse hepatocytes.

Although HDL-mediated cholesterol transport to the liver is well studied, cholesterol efflux from hepatocytes back to HDL is less well understood. Real-time imaging of efflux of 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-amino)-23,24-bisnor-5-cholen-3beta-ol (NBD-cholesterol), which is poorly esterified, and [(3)H]cholesterol, which is extensively esterified, from cultured primary hepatocytes of wild-type and sterol carrier protein-2 (SCP-2) gene-ablated mice showed that 1) NBD-cholesterol efflux was affected by the type of lipoprotein acceptor, i.e., HDL3 over HDL2; 2) NBD-cholesterol efflux was rapid (detected in 1-2 min) and resolved into fast [half time (t((1/2))) = 2.4 min, 6% of total] and slow (t((1/2)) = 26.5 min, 94% of total) pools, consistent with protein- and vesicle-mediated cholesterol transfer, respectively; 3) SCP-2 gene ablation increased efflux of NBD-cholesterol, as well as [(3)H]cholesterol, albeit less so due to competition by esterification of [(3)H]cholesterol, but not NBD-cholesterol; and 4) SCP-2 gene ablation increased initial rate (2.3-fold) and size (9.7-fold) of rapid effluxing sterol, suggesting an increased contribution of molecular cholesterol transfer. In addition, colocalization, double-immunolabeling fluorescence resonance energy transfer, and electron microscopy, as well as cross-linking coimmunoprecipitation, indicated that SCP-2 directly interacted with the HDL receptor, scavenger receptor class B type 1 (SRB1), in hepatocytes. Other membrane proteins in cholesterol efflux [SRB1 and ATP-binding cassettes (ABC) A-1, ABCG-1, ABCG-5, and ABCG-8] and several soluble/vesicle-associated proteins facilitating intracellular cholesterol trafficking (StARDs, NPCs, ORPs) were not upregulated. However, loss of SCP-2 elicited twofold upregulation of liver fatty acid-binding protein (L-FABP), a protein with lower affinity for cholesterol but higher cytosolic concentration than SCP-2. Ablation of SCP-2 and L-FABP decreased HDL-mediated NBD-cholesterol efflux. These results indicate that SCP-2 expression plays a significant role in HDL-mediated cholesterol efflux by regulating the size of rapid vs. slow cholesterol efflux pools and/or eliciting concomitant upregulation of L-FABP in cultured primary hepatocytes.

Overexpression of sterol carrier protein-2 differentially alters hepatic cholesterol accumulation in cholesterol-fed mice.

Although in vitro studies suggest a role for sterol carrier protein-2 (SCP-2) in cholesterol trafficking and metabolism, the physiological significance of these observations remains unclear. This issue was addressed by examining the response of mice overexpressing physiologically relevant levels of SCP-2 to a cholesterol-rich diet. While neither SCP-2 overexpression nor cholesterol-rich diet altered food consumption, increased weight gain, hepatic lipid, and bile acid accumulation were observed in wild-type mice fed the cholesterol-rich diet. SCP-2 overexpression further exacerbated hepatic lipid accumulation in cholesterol-fed females (cholesterol/cholesteryl esters) and males (cholesterol/cholesteryl esters and triacyglycerol). Primarily in female mice, hepatic cholesterol accumulation induced by SCP-2 overexpression was associated with increased levels of LDL-receptor, HDL-receptor scavenger receptor-B1 (SR-B1) (as well as PDZK1 and/or membrane-associated protein 17 kDa), SCP-2, liver fatty acid binding protein (L-FABP), and 3alpha-hydroxysteroid dehydrogenase, without alteration of other proteins involved in cholesterol uptake (caveolin), esterification (ACAT2), efflux (ATP binding cassette A-1 receptor, ABCG5/8, and apolipoprotein A1), or oxidation/transport of bile salts (cholesterol 7alpha-hydroxylase, sterol 27alpha-hydroxylase, Na(+)/taurocholate cotransporter, Oatp1a1, and Oatp1a4). The effects of SCP-2 overexpression and cholesterol-rich diet was downregulation of proteins involved in cholesterol transport (L-FABP and SR-B1), cholesterol synthesis (related to sterol regulatory element binding protein 2 and HMG-CoA reductase), and bile acid oxidation/transport (via Oapt1a1, Oatp1a4, and SCP-x). Levels of serum and hepatic bile acids were decreased in cholesterol-fed SCP-2 overexpression mice, especially in females, while the total bile acid pool was minimally affected. Taken together, these findings support an important role for SCP-2 in hepatic cholesterol homeostasis.

Anatomy of heat waves and mortality in Toronto: lessons for public health protection.

BACKGROUND: Periods of unusually hot weather, especially in temperate climates, carry with them a burden of morbidity and mortality, particularly in urban areas. With lessening debate on its origins, and signs of global warming already apparent, it is becoming imperative for public health practitioners to recognize and predict the risks of "heat waves", and to develop protective community responses to them. This study makes use of historical data and a methodology developed previously to examine the pattern of hot weather experienced over the last five decades in the City of Toronto, and to assess the associated burden of mortality. METHODS: Synoptic classification of air masses based on meteorological data for Toronto was used, to assign the annual mean burden of illness (in terms of elevated mortality) associated with hot weather and air pollution. Then, coefficients relating daily mortality risk to historical daily weather and air quality data were determined with a model system that (for each air mass) assessed the factors that contributed to day-to-day variability in mortality. RESULTS: Over the period of study, there were 120 (95% CI: 105-135) heat-related deaths on average per year, with great variability from year to year, reflecting the variability of hot weather. Mortality was greatest in July and August, when the greatest number of multi-day heat episodes occurred. Furthermore, the longer the episode, the greater was the daily risk for mortality. INTERPRETATION: The method can be used to forecast the risk of heat-related mortality, and to facilitate the development of public health responses to mitigate that risk.

UC/MALDI-MS analysis of HDL; evidence for density-dependent post-translational modifications.

The purpose of this study is to determine whether the nature of the post-translational modifications of the major apolipoproteins of HDL is different for density-distinct subclasses. These subclasses were separated by ultracentrifugation using a novel density-forming solute to yield a high-resolution separation. The serum of two subjects, a control with a normolipidemic profile and a subject with diagnosed cardiovascular disease, was studied. Aliquots of three HDL subclasses were analyzed by MALDI and considerable differences were seen when comparing density-distinct subclasses and also when comparing the two subjects. A detailed analysis of the post-translational modification pattern of apoA-1 shows evidence of considerable protease activity, particularly in the more dense fractions. We conclude that part of the heterogeneity of the population of HDL particles is due to density-dependent protease activity.

Electronegative LDLs from familial hypercholesterolemic patients are physicochemically heterogeneous but uniformly proapoptotic.

A highly electronegative fraction of human plasma LDLs, designated L5, has distinctive biological activity that includes induction of apoptosis in bovine aortic endothelial cells (BAECs). This study was performed to identify a relationship between LDL density, electronegativity, and biological activity, namely, the induction of apoptosis in BAECs. Plasma LDLs from normolipidemic subjects and homozygotic familial hypercholesterolemia subjects were separated into five subfractions, with increasing electronegativity from L1 to L5, and into seven subfractions according to increasing density, D1 to D7. L1 to L5 were also separated according to density, and D1 to D7 were separated according to charge. The density profiles of L1 to L5 were similar (maximum density = 1.030 +/- 0.002 g/ml). Induction of apoptosis by all seven density subfractions was confined to the highly electronegative fraction, L5, and within each density subfraction the magnitude of apoptosis correlated with the L5 content. Electronegative LDL is heterogeneous with respect to density and composition, and induction of apoptosis is more strongly associated with LDL electronegativity than with LDL size or density.

Remnant lipoprotein density profiling by CsBiEDTA density gradient ultracentrifugation.

Remnant lipoproteins (RLPs) are now considered a strong marker of the triglyceride-rich lipoprotein (TRL) class for cardiovascular heart disease. The purpose of this research is to demonstrate the efficacy of a novel method that combines an established immunoseparation assay used to measure the RLP class in human serum with ultracentrifugal density gradient separation. These two methods are combined to obtain an RLP density profile. The immunoseparation effectively removes the non-RLP lipoproteins from serum. The RLPs obtained from the immunoseparation are separated into two density-distinct fractions by ultracentrifugal density gradient separation in CsBiEDTA. It is now clear that IDL is distinct in density and immunoreactivity from the two RLP classes isolated by the immunoseparation and ultracentrifugation. This methodology defines the RLP by density and measures their relative prevalence in the TRL class. When applied to clinical samples, variations in the RLP subclasses in different patients are examined. The differences in the RLP density profile are also examined in fasting and postprandial samples. The RLP density profile significantly increases in the postprandial state versus the fasting state. However, the overall quantity of TRL does not appreciably increase in the postprandial state. This work demonstrates the feasibility of measuring the postprandial state in clinical samples to provide insight into the clearance of RLP by the liver as well as the general atherogenicity of these particles. The major outcome of this research is a novel analytical method that couples immunoseparation and density gradient ultracentrifugation to separate and differentially profile the RLP subclass against its nascent counterparts in the TRL class.

Method for lipoprotein(a) density profiling by BiEDTA differential density lipoprotein ultracentrifugation.

In this article, we demonstrate the analytical power of linking density gradient ultracentrifugation with affinity separations. Here we address some of the analytical challenges in the study of lipoprotein(a), (Lp(a)). The mean density distribution of Lp(a) was determined by a differential density lipoprotein profile (DDLP). For DDLP, the lipoprotein density distribution of a serum sample with elevated Lp(a) levels was determined by ultracentrifugation using a BiEDTA complex as a density gradient. Lp(a) was removed from a second aliquot of the same serum sample by carbohydrate affinity using wheat germ agglutinin (WGA). WGA was demonstrated to have high specificity for Lp(a) in a serum sample. This sample was ultracentrifuged to obtain a lipoprotein density distribution in the absence of Lp(a). A DDLP was obtained after subtracting the Lp(a)-depleted lipoprotein density profile from the untreated lipoprotein density profile. The DDLP methodology reported herein gives relevant information of the lipoproteins in serum such as density, isoform, and subclass characteristics. Lp(a) was quantitatively isolated from serum with a recovery efficiency of 82%. Lp(a) was purified by ultracentrifugation. Lp(a) retained its inherent density (1.086 g/mL) and immunoreactivity. The major outcome of this research was the effectiveness of using affinity separations coupled with density ultracentrifugation for the isolation of pure Lp(a) from serum and its isoform characterization based on density by DDLP.

Metal ion complexes of EDTA as solutes for density gradient ultracentrifugation: influence of metal ions.

In the study reported here, we study the nature of the metal ion complexes of EDTA as solute systems for analysis of lipoproteins by density gradient ultracentrifugation (DGU) by varying both the complexing metal ion and the counterion. Specifically, the sodium and cesium salts of complexes of Bi/EDTA, Pb/EDTA, Cd/EDTA, Fe/EDTA, and Cu/EDTA were chosen for this study. We show that useful gradients can be formed within a few hours beginning with a homogeneous solution. Data are presented that provide insight into the nature of how these gradients are formed from these complexes and how the selection of a specific complex can be used to enhance particular regions of the lipoprotein density profile for clinical studies. We also examine the use of equilibrium sedimentation theory to correlate the measured density profiles generated by these complexes with their molecular weight.

Novel truncated isoforms of constitutive serum amyloid A detected by MALDI mass spectrometry.

The main focus of the serum amyloid A (SAA) family has been on the acute phase isoforms. However, the constitutive isoform (SAA4) may have a strong effect on the metabolism of human serum lipoproteins. In this study, the SAA4 protein was examined in the high-density lipoprotein fraction of both healthy and diseased individuals. Novel isoforms of SAA4 were detected using ultracentrifugation combined with solid-phase extraction and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three truncated isoforms were identified as well as two glycosylated isoforms. Patterns of isoform distribution may be significant for assessment of cardiovascular risk as well as direction of patient treatment.

A large high-density lipoprotein enriched in apolipoprotein C-I: a novel biochemical marker in infants of lower birth weight and younger gestational age.

CONTEXT: Low birth weight is associated with increased cardiovascular disease in adulthood, and differences in the molecular weight, composition, and quantity of lipoprotein subclasses are associated with coronary artery disease. OBJECTIVE: To determine if there are novel patterns of lipoprotein heterogeneity in low-birth-weight infants. DESIGN, SETTING, AND PARTICIPANTS: Prospective study at a US medical center of a representative sample of infants (n = 163; 70 white and 93 black) born at 28 or more weeks of gestational age between January 3, 2000, and September 27, 2000. This sample constituted 20% of all infants born during the study period at this site. MAIN OUTCOME MEASURES: Plasma levels and particle sizes of lipoprotein subclasses and plasma concentrations of lipids, lipoproteins (high-density lipoprotein [HDL] and low-density lipoprotein [LDL]), and apolipoproteins. RESULTS: An elevated lipoprotein peak of a particle with density between 1.062 and 1.072 g/mL was identified using physical-chemical methods. This subclass of large HDL was enriched in apolipoprotein C-I (apo C-I). Based on the amount of the apo C-I-enriched HDL peak, 156 infants were assigned to 1 of 4 groups: 0 (none detected), 17%; 1 (possibly present), 41%; 2 (probably present), 22%; 3 (elevated), 19%. Infants in group 3, compared with those in the other 3 groups, had significantly (P<.001) lower mean birth weight (2683.7 vs 3307.1 g) and younger mean gestational age (36.2 vs 39.3 wk). After correction for age, infants in group 3 had significantly higher levels of total and large HDL cholesterol and of total and large LDL cholesterol and LDL particle number. However, infants in group 3 had lower levels of small HDL, very low-density lipoproteins, and triglycerides than infants in the other 3 groups. This lipoprotein profile differed from that in infants born small for gestational age, who had significantly higher triglyceride (P<.001) and apo B (P = .04) levels, but lower levels of total and large HDL cholesterol (P<.001) and apo A-I (P<.001). CONCLUSIONS: Because apo C-I-enriched HDL, and purified apo C-I alone, promotes apoptosis in vitro, increased amounts of this particle may have physiological significance and identify a novel group of low-birth-weight infants apparently distinct from traditionally classified small-for-gestational-age infants.