Lipid Subfractions Research Articles

English

AIM:Lipoprotein (a) and other lipid sub-fractions are known to be associated in atherosclerosis of the carotid vessels and ischemic stroke. This study was conducted to compare the specificity of variables like lipoprotein (a), HDL and LDL as independent risk factor in determining the severity and outcome of ischemic stroke.METHODS: The data for this study was collected from 50 patients of ischemic stroke who presented to KIMS hospital from June 2012 to 2013. All of who underwent clinical assessment by NIHSS score with relevant investigations, including CT scan brain, lipoprotein (a) and lipid profile.RESULTS: Male patients had higher incidence than females. Female population had higher BMI. Stroke scoring was done using NIHSS scoring;severe cases of stroke remain equal in both the sexes. The conventional risk factors were studied and were associated with severity of stroke but statistically not significant. Various lipid subfractions were studied with respect to severity of stroke and it was found that TC had p value=0.146, HDL-C p value=0.686, LDL- C p value =0.296, VLDL-C p=0.54, TG p=0.721 and Lp (a) p 150mg/dl were 2.79 times more likely to have NIHSS score>15 and patients with HDL-C 15. Low HDL-C was the only lipid abnormality seen in patients with no conventional risk factors.CONCLUSION:Ischemic stroke is associated with lipid abnormalities. Lp (a) which is genetically determined factor and HDL-C were found to be independent risk factors for predicting the outcome of ischemic stroke. Conventional risk factors were found to be less reliable. INTRODUCTION: The incidence of stroke in Indian population is difficult to estimate due to lack of accurate data. The available statistics are from urban Teaching Hospitals but these are not truly representative of the whole population as 85% of the population reside in the rural areas. According to such studies stroke constitutes about 0.9-4.5% of total hospital admissions. Ischemic strokes constitute about 57.3-82.7% of all strokes1. Cardiogenic cerebral embolism forms 15-20% of all ischemic strokes though in the younger population group <45 years it is responsible for 23-36% of strokes. Lacunar infarcts constitute about 15-20% of all ischemic strokes. 2 Once stroke has occurred, the management strategies are limited and the disability it leaves behind is often devastating. With advances in our knowledge of risk factors andprecipitating events the emphasis has now shifted to stroke prevention. Like in coronary artery disease, primary prevention can go a long way in preventing stroke. The National Institute of Health Stroke Scores (NIHSS) is a 42 point clinical examination system that has become the standard clinical severity scale in most clinical trials. 4 The scale is as follows:

Lipid abnormalities in foreign-born and US-born patients in a medical group

With an increasing foreign-born population in the United States, cardiovascular risk reduction through effective lipid treatment strategy is precluded by limited lipid profile information. This study compares the patterns of lipid abnormalities of foreign-born and US-born patients treated by a single medical group. We conducted a medical record review of 53,361 US-born and 6430 foreign-born patients in 2010. Compared with US-born, a higher proportion of foreign-born patients are younger than 40 years (26% vs 14%), receive Medicaid (24% vs 8%), and are less likely to be obese (26% vs 43%). More foreign-born patients have diabetes (25% vs 22%), are poor (4.7% vs 3.6%), and not on lipid-lowering drugs (63% vs 56%). Place of birth is not associated with total cholesterol levels. Adjusted for social and demographic characteristics, however, foreign-born are more likely than US-born to have elevated low-density lipoprotein cholesterol (adjusted difference, 2.1; 95% CI, 0.6-3.7), depressed high-density lipoprotein cholesterol (adjusted difference, 6.1; 95% CI, 4.4-7.8), and elevated triglycerides (adjusted difference, 2.4; 95% CI, 0.8-4.1). Foreign-born patients, on lipid-lowering medications, are more likely to still have elevated levels of low-density lipoprotein cholesterol (adjusted difference, 3.5; 95% CI, 1.4-5.6). Despite having a similar distribution of total cholesterol as their US-born counterparts, the other lipid fractions among foreign-born patients are more likely to be pathologic. Therefore, dyslipidemia screening tests need to include the lipid subfractions. The higher prevalence of dyslipidemias, both among foreign-born patients with and without lipid-lowering medications, challenges medical groups to intensify effective lipid treatment strategies.

Non–High-Density Lipoprotein Cholesterol and Coronary Artery Calcium Progression in a Multiethnic US Population

Non-high-density lipoprotein cholesterol (non-HDLc) is an independent predictor of cardiovascular disease risk, with elevated levels signifying an increased risk beyond low-density lipoprotein. Previous data have shown inconsistent association of lipid subfractions with progression of coronary artery calcium (CAC), a surrogate marker of incident cardiovascular disease. We sought to evaluate the association between non-HDLc and development (incident) and progression of CAC in a cohort of multiethnic asymptomatic subjects. The cohort (n = 5,705) was derived from the limited access data set of the Multi-Ethnic Study of Atherosclerosis obtained from the National Heart Lung and Blood Institute. Multivariable regression analysis was performed to derive the association between non-HDLc and incident CAC (n = 2,927) and non-HDLc and progression of CAC (n = 2,778). In the population without CAC at baseline, non-HDLc, especially >190 mg/dl, was independently associated with incident CAC (relative risk 1.40, 95% confidence interval 1.09 to 1.79, p = 0.008) after adjustments with age, gender, race, systolic blood pressure, antihypertension medication use, smoking, diabetes, lipid-lowering therapy use, follow-up duration, and waist-hip ratio. Similarly, among those with CAC at baseline, non-HDLc levels >190 mg/dl were associated with significant CAC progression in the overall population (β 16.4, 95% confidence interval -5.63 to 27.2, p = 0.003) after adjustments. In conclusion, non-HDLc levels, especially >190 mg/dl, are consistently associated with increased risk of CAC progression. Our results suggest that among lipid fractions, non-HDLc may be best suited for the prediction of future CAC progression.

ULTRASONOGRAPHIC CHARACTERISTICS OF LIPIDURIA IN CLINICALLY NORMAL CATS

Echoes are frequently seen in the urinary bladder of cats during abdominal ultrasound. These have been attributed to hematuria, pyuria, crystalluria, and lipid. However, sonographic findings have not been previously correlated with urinalysis. We prospectively evaluated 40 clinically normal cats via ultrasound, serum chemistry, and urinalysis. Thin layer chromatography was performed on the urine to determine the amount (mg) of lipid subfractions including diacylglycerol, triglyceride, phospholipid, free fatty acid, cholesterol, and cholesterol ester. Ninety percent (36/40) of the cats in our population had sonographic echoes suspended in the urinary bladder, with most having a subjective score of mild echoes (n = 20). None of the sonographic echoes were gravity dependent or caused distal acoustic shadowing, reverberation, or twinkle artifact. Of the cats with sonographic echoes in the urine, 66% (24/36) had no significant findings on urinalysis other than the presence of lipid. The total amount of subjective sonographic echoes was not significantly related to the total amount of fat measured on thin layer chromatography or the number of lipid droplets seen on urinalysis. An increased amount of urine diacylglycerol was significantly associated with clumping of echoes (P = 0.02) and the amount of lipid droplets seen on urinalysis (P = 0.04). An association between increased amounts of urine diacylglycerol and the amount of echoes seen on ultrasound approached significance (P = 0.05). Findings from this study support previously published theories that sonographic echoes within the urinary bladder of clinically normal cats may be due to urine lipid.

Longitudinal associations between serum cholesterol levels and suicidal ideation in an older Korean population

IntroductionRelationships between low total cholesterol levels and suicidality have been reported but there has been little investigation of this issue in older age groups. This study aimed to investigate longitudinal associations between serum lipid levels and suicidal ideation in an older population. Methods732 community dwelling elderly aged 65 or over were evaluated at baseline. Of 639 did not have suicidal ideation at baseline, 579 (90.6%) were followed two years later. Prevalence and incidence of suicidal ideation within the previous one month was ascertained. Serum levels of total-, high density lipoprotein (HDL)-, low density lipoprotein (LDL)- cholesterol, and triglycerides were assayed at both baseline and follow-up. Baseline data on potential covariates including sociodemographic characteristics, life stress, social support, pain, alcohol drinking, depressive symptoms, cognitive function, and disability were gathered. ResultsBoth higher and lower total and LDL cholesterol levels at baseline and a decline in total cholesterol levels over the follow-up period predicted an increased incidence of suicidal ideation at follow-up independent of sociodemographic and clinical covariates. Significant cross-sectional associations were found between suicidal ideation at baseline and higher total and LDL cholesterol levels. LimitationsSuicidal ideation was the outcome of the study. Therefore generalizability should be considered. ConclusionsThese results support a role of dyslipidemia in the etiology of late-life suicidal ideation. Not only low but also higher cholesterol levels predicted the incidence of suicidal ideation in elders. Lipid sub-fraction assays might be informative in this respect at least in older populations.

Effects of Resveratrol in Patients with Type 2 Diabetes Mellitus on Skeletal Muscle SIRT1 Expression and Energy Expenditure

The primary aims of the study were to examine the effect of resveratrol on skeletal muscle SIRT1 expression and energy expenditure in subjects with Type 2 diabetes mellitus (T2DM). Animal and in vivo studies indicate that resveratrol increases SIRT1 expression that stimulates PGC1α activity. Subsequent upregulation of AMPK and GLUT4 expression are associated with improved insulin sensitivity in peripheral tissues. Ten subjects with T2DM were randomized in a double-blind fashion to receive 3g resveratrol or placebo daily for 12 weeks. Secondary outcomes include measures of AMPK, p-AMPK and GLUT4 expression levels, energy expenditure, physical activity levels, distribution of abdominal adipose tissue and skeletal muscle fiber type composition, body weight, HbA1c, plasma lipid subfraction, adiponectin levels, and insulin sensitivity. There was a significant increase in both SIRT1 expression (2.01 vs. 0.86 arbitrary units [AU], p = .016) and p-AMPK to AMPK expression ratio (2.04 vs. 0.79 AU, p = .032) in the resveratrol group compared with the placebo group. Although the percentage of absolute change (8.6 vs. -13.9%, p = .033) and percentage of predicted resting metabolic rate (RMR; 7.8 vs. -13.9%, p = .013) were increased following resveratrol, there was a significant reduction in average daily activity (-38 vs. 43.2%, p = .028) and step counts (-39.5 vs. 11.8%, p = .047) when compared with placebo. In patients with T2DM, treatment with resveratrol regulates energy expenditure through increased skeletal muscle SIRT1 and AMPK expression. These findings indicate that resveratrol may have beneficial exercise-mimetic effects in patients with T2DM.

Development of an MRM assay panel with application to biobank samples from patients with myocardial infarction

As part of a Swedish national cardiological research initiative, the development of a quantitative MRM assay is reported for the quantification of eleven putative cardiovascular disease markers. Within the study, patient samples from the LUNDHEARTGENE biobank were processed and nanoLC-MS/MS analysis was performed together with a stable isotope dilution strategy for absolute quantification of the target proteins. Excellent linear regressions were achieved for 9 of the 11 peptides with LOQ ranged in the attomolar range. We have utilized the assay for the screening of plasma samples from patients with chest pain, and performed a comparative analysis of patients with ST-segment elevation myocardial infarction and chest pain due to other causes. The assay demonstrates high reproducibility and correlate with clinical findings. Strong correlations were found for several of the apolipoproteins and their respective lipid subfractions (LDL, HDL or triglycerides). APOC1, APOC2 and APOE were elevated in patients with STEMI. An MRM assay were developed for putative cardiovascular disease markers as target proteins, and applied to biobanking sample material. The comparative analysis of patients with ST-segment elevation myocardial infarction and chest pain due to other causes showed elevated levels of APOC1, APOC2 and APOE in patients with STEMI. These observations raise interesting novel hypotheses about the role of apolipoproteins C1, C2 and E in the pathophysiology of acute myocardial infarction, which merits further studies.

Low-density lipoprotein subfraction, carotid artery intima-media thickness, nitric oxide, and tumor necrosis factor alpha are associated with newly diagnosed ischemic stroke

Objectives:Small dense (sd) low-density lipoprotein (LDL), tumor necrosis factor (TNF) alpha (α), and nitric oxide (NO) have recently emerged as important stroke risk factors. The aim of the study was to investigate the effects of increased levels of small LDL particle size, TNF-α and NO on the developed ischemic stroke and increased carotid artery intima-media thickness (CIMT).Materials and Methods:A total of 29 women and 25 men (a total of 54 ischemic stroke patients) and a similar age group of 50 controls (29 females and 21 males) were included in the study. CIMT, C-reactive protein (CRP), TNF-α, NO, and lipid subfraction test of the two groups were measured.Results:The mean LDL particle size was smaller in patients with stroke than in the controls (26.8 ± 0.31 nm vs. 27.0 ± 0.31 nm, P = 0.003). sd-LDL, TNF-α, NO, CRP, right CIMT, and left CIMT were higher in patients with stroke than in the controls (respectively; 8.2 ± 7.8 mg/dL vs. 3.3 ± 3.5 mg/dL, P < 0.001;75.6 ± 25.0 pg/mL vs. 65.4 ± 9.1 pg/mL, P = 0.009;76.4 ± 53.3 mmol/L vs. 41.5 ± 27.0 mmol/L, P < 0.001;1.9 ± 2.6 mm vs. 0.4 ± 0.3 mm P < 0.001;0.97 ± 0.38 mm vs. 0.83 ± 0.15 mm, P = 0.007;1.04 ± 0.44 mm vs. 0.87 ± 0.19 mm, P = 0.010).Conclusion:These results show that sd-LDL is independently associated with the incidence of stroke and may be a risk factor in the development of stroke. In addition, TNF-α, NO, right CIMT, and left CIMT may be a risk factor in the development of ischemic stroke.

Serum calcitonin gene-related peptide levels in women with polycystic ovary syndrome

Calcitonin gene-related peptide (CGRP) is an amino acid neuropeptide with widespread expression. It has potent effects on lipid and energy metabolism. It induces insulin resistance. This study was planned to determine CGRP levels in women with polycystic ovary syndrome (PCOS). Forty-seven women with PCOS and 34 healthy controls were evaluated in this controlled clinical study. Serum lipid sub-fractions, postprandial and fasting glucose, insulin and other hormones (gonadotropins, androgens) and CGRP levels were measured. Homeostasis model assessment (HOMA-IR) was used to estimate insulin resistance. Waist measurements, postprandial and fasting glucose and fasting insulin levels and free androgen index and HOMA-IR were significantly higher in subjects with PCOS. However, the women with PCOS had considerably lower high-density lipoprotein cholesterol levels than healthy subjects. Serum CGRP levels were higher in study subjects than in controls, although it was statistically insignificant. Serum CGRP level was not related with insulin resistance, ovarian hyperandrogenism and dyslipidemia in abdominally obese women with PCOS. These outcomes propose that CGRP may not play a pivotal role in the pathogenesis of PCOS.

Selenium and lipid subfractions in Egyptian type 2 diabetes patients

The purpose of this study was to examine the relationship between serum selenium (Se) levels and lipid subfraction among Egyptian type 2 diabetes patients and their association with the severity of the disease. The study was conducted on 60 type 2 diabetic adults with BMI <30 divided according to disease duration into two groups: group 1 with disease duration less than 5 years and group 2 with a disease duration more than 5 years. Thirty age- and sex-matched apparently healthy volunteers were considered as the control group. Serum selenium was measured by atomic absorption spectrometry lipid subfractions including small dense low density lipoprotein (sd LDL) which was measured by enzyme-linked immunosorbent assay and glycated hemoglobin (HbA1c) by high-performance liquid chromatography. All participants do not receive Se supplementation. The mean serum Se level in participants with diabetes was as follows: group 2 = 62.70 ± 5.73, group 1 = 70.58 ± 4.158, and control subjects = 79.80 ± 5.37 μg/l (p = 0.00). Se was found to be an independent protective factor with an OR of 0.29 and 95 % CI of 0.06–1.3. Mean serum sd LDL in participants with diabetes was as follows: group 2 = 43.81 ± 13.70, group 1 = 25.77 ± 5.28, and control group = 15.99 ± 5.32 (p = 0.00). Correlation study, between studied parameters, revealed positive correlation between sd LDL and apolipoprotein B (Apo B) (r = 0.730, p = 0.001). On the other hand, negative correlation was encountered between apolipoprotein A (Apo A) and Apo B (r = −0.514, p = 0.001) as well as Apo A and sd LDL (r = −0.697, p = 0.001). Selenium correlated negatively with both Apo B (r = −0.669, p = 0.001) and sd LDL (r = −0.671, p = 0.001) and positively with Apo A (r = 0.513, p = 0.001). In a sample of the Egyptian population, low serum Se levels were positively associated with the prevalence of diabetes. Until findings from prospective studies and randomized controlled trials are available, Se intake, including Se supplementation, should be recommended for primary or secondary diabetes prevention in populations with inadequate selenium status.

Commentary: Shaper and Jones, 'Serum-cholesterol, diet and coronary heart-disease in Africans and Asians in Uganda': 50-year-old findings only need interpretational fine tuning to come up to speed!

Commentary: Shaper and Jones, 'Serum-cholesterol, diet and coronary heart-disease in Africans and Asians in Uganda': 50-year-old findings only need interpretational fine tuning to come up to speed!

Atherogenic low density lipoprotein phenotype in long-term survivors of childhood acute lymphoblastic leukemia

Survivors of childhood acute lymphoblastic leukemia (ALL) have an increased risk of cardiovascular disease. Small density lipoproteins are atherogenic but have not been studied in this population. We conducted a cross-sectional analysis of 110 ALL survivors (mean age, 24.3 years) to determine prevalence of small dense LDL (pattern B) phenotype in ALL survivors and identify associated factors. Lipid subfractions were measured using Vertical Auto Profile-II. Participants with greater than 50% of LDL-cholesterol (LDL-c) in small dense LDL fractions (LDL(3+4)) were classified as LDL pattern B. Visceral and subcutaneous adipose tissue (VAT, SAT) volumes were also measured by computed tomography. While the mean LDL-c level of ALL survivors was 108.7 ± 26.8 mg/dl, 36% (40/110) of survivors had atherogenic LDL pattern B. This pattern was more common in males (26/47; 55%) than in females (14/63; 22%, P = 0.001) and more common in survivors treated with cranial radiotherapy (15/33; 45%) than in those who were treated with chemotherapy alone (25/77; 33%; P = 0.04, adjusted for age, gender, history of hypertension, and smoking history). VAT was associated with atherogenic lipids: LDL pattern B and LDL(3+4) levels. This association was independent of other measures of body fat. We conclude that a substantial proportion of ALL survivors had an atherogenic LDL phenotype despite normal mean LDL-c levels. An atherogenic LDL phenotype may contribute to the increase in cardiovascular mortality and morbidity in this population.

Lipoprotein Subfractions by Ion Mobility in Lean and Obese Children

To establish normative data for lipoprotein subfractions using a novel ion mobility assay in healthy lean children and to compare their data with those of obese children preselected with normal glucose, blood pressure, and relatively normal lipids. Fasting blood samples in 162 children aged 7.0-18.9 years (75 lean [body mass index: 18.6 ± 6.6 kg/m(2)] and 87 obese [body mass index: 31.7 ± 5.4 kg/m(2)]) were analyzed. Correlation of lipoprotein subfractions with anthropometric and laboratory markers was performed. Principal component analysis was used to avoid using correlated variables. Normative data for lipid subfractions were obtained in healthy children. Lean children had higher high-density lipoprotein (HDL)-large (76%), HDL-small (13%), and HDL-total (27%) compared with obese (P < .01), and lower low-density lipoprotein (LDL)-medium (-30%, P < .01) and medium + small (-21%, P = .02) as well as LDL-total (-13%, P = .035). In both groups, the LDL component was higher in males and pubertal children (P < .01). Prepubertal children had a higher HDL component than pubertal ones (P < .004). Adjusting for sex and pubertal status LDL component was positively, and HDL component negatively, correlated with obesity (P < .004). Despite relatively normal triglycerides and cholesterol measured with standard assays at screening, ion mobility analysis showed significant differences in lipid and apolipoprotein subfractions between lean and obese children, even those prepubertal. Long-term, prospective follow-up may better characterize the predictability of lipid subfractions for future cardiovascular disease risk in children.

Association of Lipid Subfractions and Cardiovascular Events in Women

Atherogenic lipoproteins include very-low-density, low-density, and intermediate-density particles, each of which carries an apolipoprotein B molecule.

Waist circumference is a strong and independent determinant of the distribution of HDL subfractions in overweight patients with cardiovascular risk factors

Our aim was to determine the influence of waist circumference on the repartition of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) subfractions in patients with increased waist perimeter and one or more cardiovascular risk factor. All 117 patients without lipid-lowering therapy underwent routine clinical, biological evaluation and isolation of the following lipid subfractions: HDL2b, HDL2a, HDL3a, HDL3b, HDL3c and LDL1, LDL2, LDL3, LDL4. Mean waist circumference was 102.9 cm for women and 109.4 cm for men, and 92 patients presented with metabolic syndrome. In the highest waist circumference tertile, when compared with the lowest one, an increased HDL3c (7.7% vs. 5.7% p=0.02) and a non-significant decrease of HDL2b percentages were observed with no difference in other subfractions. In multivariate analysis, only plasma triglycerides and waist circumference remained independent predictors of HDL3c percentage. In our population, waist circumference was a strong and independent determinant of a shift in the distribution of HDL toward denser particles.

Polikistik Over Sendromlu Kadınlarda Dolaşımdaki Tip 1 Kolajen C-Terminal Propeptid Düzeyleri

Objective: Collagen type I is abundant in the outer layers of capsular stroma and theca externa in the ovary. C-terminal propeptide of Type I collagen (CICP) is the measurable form of type I procollagen in serum. Circulating CICP levels are indicative of collagen production. This study was designed to determine the serum levels of CICP and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels in women with Polycystic Ovary Syndrome (PCOS). Material and Methods: This study included twenty-five women with PCOS in the study group and twenty healthy women in the control group. Serum lipid sub-fractions, fasting glucose and insulin, hormone (gonadotropins, androgens), CICP and TIMP-1 levels were measured. Homeostasis model assessment (HOMA-IR) was used to estimate insulin resistance. Results: Serum luteinizing hormone (LH) and fasting insulin levels, LH/follicule stimulating hormone (FSH) ratio, free androgen index (FAI) and HOMA-IR values were higher in patients with PCOS compared with healthy women. A significant increase in CICP level was observed in subjects with PCOS, and TIMP-1 level was found to be significantly decreased. HOMA-IR value was positively correlated with CICP level, but inversely with TIMP-1 level. The best cut-off values for CICP and TIMP-1 were >49.94 ng/mL (sensitivity 92.6% and specificity 65%) and <275.99ng/ml (sensitivity 92.6% and specificity 40%) respectively. Conclusion: Elevated circulating CICP levels may be associated with thickened tunica albuginea in women with PCOS. However, the exact role of CICP in the pathogenesis of the disease remains to be elucidated.

Treatment of Hypertriglyceridemia With Fibric Acid Derivatives: Impact on Lipid Subfractions and Translation Into a Reduction in Cardiovascular Events

This review investigates how the treatment of hypertriglyceridemia with fibric acid derivatives impacts lipid concentrations, lipid particle size, and the rate of cardiovascular events: expressly, to decide whether the use of fibric acid derivatives is an effective treatment option in the reduction of cardiovascular endpoints for patients with specific lipid parameters at baseline. Fibric acid derivatives reduce fasting triglyceride (TG) values by 15% to 50% (depending on baseline level) and low-density lipoprotein cholesterol (LDL-C) by 8%, and raise high-density lipoprotein cholesterol (HDL-C) by 9%. In conjunction with a statin, the amount of TG lowering is approximately doubled with the addition of the fibrate. When measured, fibrates decrease the TG concentration of very low-density lipoprotein cholesterol particles while increasing the TG content of LDL particles. The mean size of LDL particles increases and there is a substantial reduction in the number and proportion of small, dense LDL. In randomized trials in primary and secondary prevention populations, fibrates were associated with a significant reduction in nonfatal myocardial infarction in most studies. In the subgroup with elevated TG and/or depressed HDL-C at baseline, all trials have found statistically significant relative risk reductions of 27% to 65% in the primary cardiovascular endpoint of myocardial infarction and cardiovascular death.

Relative importance of different lipid risk factors for the development of myocardial infarction at a very young age (≤ 40 years of age)

Low-density lipoprotein (LDL) cholesterol lowering has been established as one of the principal targets in preventive cardiology. Recently, assessment of LDL particle size and number as well as other lipid moieties has been presented as a more reliable method to quantify atherogenicity of the lipoprotein fractions. Thus, it was our aim to assess the influence of different lipoprotein fractions on premature myocardial infarction (≤ 40 years of age). We enrolled 302 patients into our multicentre case-control study, including 102 patients with myocardial infarction and 200 age-, gender- and centre-matched controls. The LDL and HDL Lipoprint System were used for lipid subfraction quantification. The lipid risk factors most strongly associated with premature acute myocardial infarction (AMI) in the adjusted model were non-HDL C (OR 5·02, 95% CI 2·75-9·15, P-value = 0·001), LDL-C (OR 4·35, 95% CI 2·5-7·57, P-value = 0·001), VLDL-C (OR 3·66, 95% CI 2·14-6·28, P-value = 0·001), large IDL-C (OR 3·15, 95% CI 1·94-5·12, P-value = 0·001), large LDL-C (OR 3·67, 95% CI 2·19-6·15, P-value = 0·001) and intermediate LDL-C (OR 1·96, 95% CI 1·25-3·06, P-value = 0·003). In contrast, small dense LDL was not significantly associated with premature myocardial infarction. Non-HDL cholesterol is most strongly associated with premature coronary artery disease and could serve as preferred risk predictor and therapeutic target in this young patient population (≤ 40 years). Besides, VLDL, LDL-C, large LDL, intermediate LDL and large IDL were significantly associated with premature myocardial infarction. Furthermore, our data suggest that risk prediction using small dense LDL particles might not be useful in young AMI survivors.

Lipoprotein Subfractions and Particle Size in End-Stage Renal Disease

It is interesting to note that the most heavily relied upon measures in nephrology and cardiology are both derived from calculations based on laboratory and clinical values, that is, the estimated GFR and the estimated concentration of low-density lipoprotein cholesterol (LDL-C). The actual particles of LDL in the bloodstream represent the end product of multiple hydrolysis steps that allow the initial nutritional packet, very low-density lipoprotein (VLDL), to deliver fatty acids, as well as cholesterol esters, to tissues for cellular metabolism and maintenance. The half-life of LDL is approximately 3 days, and it is believed that LDL itself has no nutritional value (1). In an ideal situation, LDL would meet its catabolic fate by docking with the LDL receptor and clearance from the circulation. However, in most adults, there is an age-related increase in LDL-C due to impaired clearance and perhaps recirculation of particles via cholesteryl esterase transfer protein. Smaller LDL particles have a longer clearance time and are more densely packed with cholesterol ester than larger particles, giving them more opportunity for tissue deposition (Figure 1) (1). While LDL-C has served reasonably well as an estimate and a proxy for the pathogenic LDL particles, many have believed that measurement of either the number or concentration of particles according to size, or determination of the apolipoprotein B concentration (1:1 with the number of LDL particles) should bring us closer to appreciating ongoing deposition of LDL into the vessel wall, advancing atherosclerosis, and translation into binary events such as myocardial infarction and cardiovascular death (2,3). Figure 1. Depiction of smaller dense LDL particles with ingress into the subintimal space initiating the pathogenesis of atherosclerosis. HSPG, heparin sulfate proteoglycans. In this issue of the journal, Noori and colleagues performed detailed LDL particle analysis on a random sample (n = 235) of hemodialysis patients who were part of a well established cohort followed for all-cause mortality (4). One of the most striking findings in this study is the influence of obesity, as stratified above and below a body mass index of 27 kg/m2, which was associated with an approximately 20 to 40% increase in triglycerides, and statistically significantly higher LDL-C, total LDL particles, and very small to medium LDL particles. The very small LDL particles were only significantly correlated (R = 0.21) with one nonlaboratory measure: fat mass percent. This influence of excess adiposity on lipid subfractions in end-stage renal disease (ESRD) appear to be greater than those observed in the general population (5). These relationships are important to remember, as the detailed tables and figures in this article suggest that there are modest relationships between small LDL particle number and concentration with all-cause mortality, which is a relatively crude and diluted proxy for translated atherosclerotic events. Thus, this article indirectly brings into focus, perhaps, a special pathogenicity of excess adiposity in patients with chronic uremia that is related, in part, to greater numbers of smaller LDL particles. These nuances are fairly well concealed in the standard lipid profile, which features the calculated LDL-C. Many articles suggest that chronic kidney disease (CKD), independent of other risk factors, appears to accelerate the atherosclerotic process, including the gradient dependent deposition of LDL particles, recruitment of monocytes, upregulation of adhesion molecules, ingress of monocytes and conversion to macrophages and foam cells, oxidation of lipid material, mobilization of vascular smooth muscle cells, breakdown of the elastic lamina, and development of an atheroma, which expands both toward the lumen and outward toward the adventitia (6–8). The most prominent component of atherosclerosis influenced by CKD is calcification, which, interestingly, is not associated with LDL particle size or number, nor is it influenced by lipid-lowering therapy (9,10). The present article by Noori and coworkers suggests that, beyond calcification, an atherogenic dyslipidemia is more prominently related to excess adiposity and is in the causal for pathway for earlier, more severe, and consequential atherosclerosis in patients with ESRD (11–13). Future research in ESRD using advanced clinical lipidology measures, including oxidized lipids and quantity, size, content, and circulatory time of particles, is warranted. More detail will be needed on the effects of adiposity, concurrent medications, and state of vascular disease determined by imaging. Finally, the end points of future studies will deserve to be more focused on atherosclerotic vascular events that experts can adjudicate and agree upon, including unstable angina, acute myocardial infarction, and ischemic stroke. The clinical use of commercially available lipoprotein subfractionation or particle tests in patients with ESRD is premature at the present time, due to the complexity of the biologic relationships in uremia, degree of uncontrolled confounding, lack of harmony between testing methodologies on the market, and the absence of a clear therapeutic mandate above and beyond what we currently have in the conventional lipid profile (14).

Niacin Is Ineffective in Patients with Established Cardiovascular Disease

Physicians sometimes prescribe niacin for statin-treated patients to raise HDL cholesterol levels or to manipulate lipid subfractions detected by more