Sd LDL Research Articles

Small dense low density lipoprotein predominance in patients with type 2 diabetes mellitus using Mendelian randomization.

Patients with T2DM often suffer from CVD-related complications, significantly impacting morbidity and mortality rates. The upsurge in CVD prevalence among them is partly linked to sd LDL particles. Understanding the mechanisms behind elevated sd LDL levels is critical for preventing and managing cardiovascular complications in diabetes. MR was employed to identify instrumental variables and establish causality, exploring underlying mechanisms. Notably, T2DM itself, insulin resistance, and fasting glucose seemingly do not directly impact sd LDL levels. Instead, the presence of T2DM or insulin resistance, leading to reduced HDL cholesterol or elevated TG levels, directly contributes to subsequent sd LDL increases, indicating a comprehensive mediating effect. While LDL cholesterol levels correlate positively with sd LDL, they appear unaffected by T2DM or insulin resistance. Importantly, hypertension induced by T2DM or insulin resistance exhibits a positive effect on sd LDL reversal. Unlike T2DM or insulin resistance, blood glucose levels show no significant impact on all processes. It is hoped that these insights might influence the treatment of patients with diabetes and the management of blood parameters in clinical practice. Examining the effect of T2DM or insulin resistance on sd LDL within HDL cholesterol and triglycerides pathways might provide valuable insights for targeted cardiovascular treatments. Additionally, the study's exploration of the potential positive effects of elevated blood pressure on sd LDL reversal may introduce novel considerations for blood pressure management in patients with diabetes.

Frequency of Metabolic Syndrome and Lipid Profile Analysis among Patient with Type 2 Diabetes: A Single Center Study

Background: Diabetes mellitus is associated with various metabolic disorders, which leads to the progression of the disease and its complications. Dyslipidemia has been noted to play an integral role in the pathogenesis and progression of micro and macro vascular complications in diabetes mellitus (DM) patients. Lipid profile is the indicators of dyslipidemia. Aim of the Study: The aim of this study was to accumulate the frequency of metabolic syndrome and lipid profile among patient with type 2 diabetes. Methods: This hospital based descriptive type of observational study was conducted in the Department of Medicine, North Bengal Medical College and Hospital, Sirajgonj, Bangladesh during the period from January 2022 to December 2022. In total 97 diagnosed patients with type 2 diabetes mellitus were enrolled in this study as the study subjects. Proper written consents were taken from all the participants before data collection. All demographic as well as clinical data were recorded. Data were processed, analyzed and disseminated by using MS Excel and SPSS version 23.0 program as per necessity. Results: The highest number (37%) of our participants was from 41-50 years’ age group and the female participants were dominating in number. Majority of the patients (63%) were obese: ≥30. In this current study, the frequency of metabolic syndrome was found as 71%. The mean± SD total cholesterol, triglyceride, LDL cholesterol and HDL cholesterol of the respondents were found as 179.88±42.81, 179.88±42.81, 109.74±46.69 and 44.75±7.68 mg/dL respectively. Among the majority of our patients (72%) normal (≥40 mg/dL) HDL level was found. Conclusion: The higher frequency of metabolic syndrome among type 2 diabetes patients demands more attention from health professionals as well as the policy makers. There may not have any significant correlation of metabolic syndrome or type 2 diabetes with lipid profile but aged people may be prone to those diseases.

Level of non-conventional lipid parameters and its comparative analysis with TSH in subclinical hypothyroidism.

The objective of this study is to estimate lipid parameters in subclinical hypothyroidism and correlate it with TSH. Forty newly diagnosed cases of subclinical hypothyroidism and Forty age and gender-matched healthy controls were recruited for the study. Blood samples were collected from them and serum lipid profile (i.e. HDL, LDL, TG, serum total cholesterol) of the subjects was estimated by standard photometric methods in a fully auto-analyzer (MINDRAY BS-300) using commercially available kits and VLDL cholesterol was calculated using the Friedewald's formula. While serum Ox-LDL, Lipoprotein A, Apolipoprotein A1 and Apo B were estimated by using commercial kit based on enzyme-linked immmunosorbent assay. The parameters such as Oxidized low-density lipoprotein (Ox-LDL), lipoprotein (a), apolipoprotein A1, apolipoprotein B and small dense lipoprotein (sd LDL) were significantly increased in subclinical hypothyroid cases when compared with the control subjects (p<0.0001). In present study results showed significant positive correlations of serum thyroid stimulating hormone (TSH) with Ox-LDL (r=0.85, p<0.01), sd LDL (r=0.71, p<0.01). The present study focuses on the role of Ox-LDL, sd-LDL Lipoprotein A, Apolipoprotein A1 and Apo B that are sensitive indicators of atherogenic dyslipidemia in subclinical hypothyroidism and can serve as a better & novel risk factor for CAD.

Reduction in Serum LDL Cholesterol Using a Nutrient Compendium in Hyperlipidemic Adults Unable or Unwilling to Use Statin Therapy: A Double-Blind Randomized Crossover Clinical Trial

BackgroundMany hyperlipidemic patients prescribed β-hydroxy-β-methylglutaryl coenzyme A reductase inhibitors (statins) are unable or unwilling to take them. A hedonically acceptable snack-based solution formulated from cholesterol-lowering food ingredients could represent a therapeutic alternative but has not been tested in this population. ObjectivesTo evaluate the effect of snacks containing a compendium of functional bioactives on fasting LDL cholesterol in statin candidates unwilling to use or intolerant to ≥1 statin drug. Secondary outcomes included changes in circulating total cholesterol (TC), triglycerides, HDL cholesterol, fasting glucose, insulin, and high-sensitivity C-reactive protein concentrations, as well as effects of single-nucleotide polymorphisms (SNPs) on outcome. MethodsThis multicenter, randomized, double-blind, free-living crossover study was composed of 2 regimented phases of 4 wk each, separated by a 4-wk washout. Eighteen men and 36 women, with a mean ± SD age of 49 ± 12 y and mean ± SD LDL cholesterol of 131 ± 32.1 mg/dL, were instructed to ingest a variety of ready-to-eat snacks twice daily as a substitute for something they were consuming already. Other behavior changes were actively discouraged. Treatment products provided ≥5 g fiber, 1000 mg ω-3 (n–3) fatty acids, 1000 mg phytosterols, and 1800 μmol antioxidants per serving. Control products were calorie-matched like-items drawn from the general grocery marketplace. Serum lipids were measured at baseline and the end of each phase and compared using the ANOVA model. Compliance to study foods was confirmed by serum 18:3n–3 concentration assessment. ResultsComparing intervention phase endpoints, LDL cholesterol was reduced a mean ± SD of 8.80 ± 1.69% (P < 0.0001), and TC was reduced a mean ± SD of 5.08 ± 1.12% (P < 0.0001) by treatment foods compared with control foods, whereas effects on other analytes did not differ between treatments. SNPs were not significantly related to outcomes (P ≥ 0.230). Compliance with study foods was 95%. ConclusionsConsumption of hedonically acceptable snacks containing a compendium of cholesterol-lowering bioactive compounds can rapidly and meaningfully reduce LDL cholesterol in adult patients unable or unwilling to take statin drugs. This trial was registered at clinicaltrials.gov as NCT02341924.

Non-HDL as a Valid Surrogate Marker of Small Dense LDL in a Young Indian Population.

Small dense (sd) LDL is a significant independent risk factor for premature coronary artery disease (CAD). Unfortunately, its estimation is not popular, due to the limited availability of specialized equipment, high cost and time-consuming technique. Non-HDL is a calculated, single index measure of all atherogenic apolipoprotein-B containing lipoproteins. This study aimed at identifying non-HDL as a superior surrogate marker of sdLDL cholesterol in a young Indian population. 161 healthy subjects < 45years were tested for lipid profile, apolipoproteins A1 and B, and sdLDL particle size. sdLDL particles showed negative correlation with non-HDL (r = - 0.283, p < 0.001), LDL (r = - 0.195, p = 0.013) and apoB/apo A1 (r = - 0.175, p = 0.026), the significance being greatest with non-HDL. ROC showed AUC for non-HDL, LDL and apoB/apo A1 as 0.704, 0.686, and 0.596 respectively. For LDL < 130mg/dL, sdLDL showed a more significant negative correlation with non-HDL (r = - 0.291, p < 0.001) as compared with apoB/apoA1 (r = - 0.172, p = 0.037). For triglycerides < 200mg/dL, sdLDL particle size showed higher significant negative correlation with non-HDL (r = - 0.213, p = 0.015) than with LDL (r = - 0.176, p = 0.045) while for triglycerides between 200 and 400mg/dL, significant negative correlation was observed only with non-HDL (r = - 0.372, p = 0.043). Hence, our study suggested that non-HDL is a superior surrogate marker of sdLDL particle size as compared to LDL and apoB/A1 ratio in a young healthy Indian population and should be used for optimum assessment of dyslipidemias and CAD risk.

PEMERIKSAAN TINGKAT sdLDL SERUM SEBAGAI PETANDA DIAGNOSTIK STENOSIS KORONER (Serum sdLDL Level as A Diagnostic Marker of Coronary Stenosis)

Small dense LDL (sdLDL) is the LDL which particles are small and dense, it is pro-atherogenic. Increased levels of serum sdLDL areassociated with an increased risk of coronary stenosis. The aim of this study was to examine the diagnostic value of sd LDL in coronarystenosis. An analytical observational study with cross sectional approach was conducted at the Department of Clinical Pathology, MedicalFaculty of Diponegoro University/Dr. Kariadi Hospital and the Unit of Cardiac diseases during the period of March-October 2013. Thesubjects were 39 patients suspected of suffering a coronary stenosis. The diagnosis of coronary stenosis, degree of stenosis and numberof vascular stenosis was established at the time of cardiac catheterization. SdLDL assessment used a test kit. The statistical analysis usedwere unpaired t-test, Spearman correlation test, ROC analysis and diagnostic test. LDL levels in stenosis subjects, 35.4±9.01 mg/dL weresignificantly higher compared to levels in subjects that had no stenosis, 20.7±7.10 mg/dL (p&lt;0.001; unpaired t-test). Correlation testresults showed a correlation between levels of serum sdLDL with severe degree of stenosis (correlation coefficient -0.64, p &lt;0.001) and amoderate positive correlation between the number of vascular stenosis (Coefficient correlation 0.46; p=0.003; Spearman Correlation'sTest). The area under the curve of ROC was 0.9 (p &lt;0.001). The cut off levels sdLDL were used to detect stenosis. The results showeda sensitivity of 85.2%, specificity of 75%, positive predictive value of 88.5%, negative predictive value of 69.2% and accuracy of 82%.Levels of serum sdLDL were associated with severe to extensive stenosis degree, and showed a good diagnostic value, thus, it can beused for screening to determine the presence of coronary stenosis.

Correlation of Atherogenic Indices and IMA with Glycaemic Control in Diabetic Patients with and without Dyslipidemia

Atherosclerosis is one of the most common major complications associated with type 2 diabetes mellitus. Recent research suggests that the major culprits are modified proteins like LDL and albumin. Hence, this study focuses on the analysis of small dense LDL (sd LDL), oxidised LDL (ox LDL) and ischemia modified albumin (IMA) in type 2 diabetes mellitus patients with and without dyslipidemia and compare with healthy subjects. Further, correlate atherogenic indices (ox LDL/HDL and sdLDL/HDL) with glycated haemoglobin in these groups. 90 subjects aged between 30-60 years of both the genders were divided into 3 groups namely diabetic dyslipidemia (Group1), diabetic non dyslipidemia (Group2) and normal (group3). Serum lipid profile, ox LDL and IMA were estimated by spectrophotometric methods, sd LDL by calculation and glycated Hb by HPLC. Ox LDL showed an apparent increase in diabetics (group 1and 2) compared to normal. Though sd LDL levels in diabetic patients remained normal, the values doubled in dyslipidemic diabetics. sd LDL/HDL ratio was significantly high in both group1and 2 compared to normal. Furthermore, there was a significant positive correlation of this ratio with glycated Hb in both groups of diabetes. Serum IMA also increased significantly in diabetes with dyslipidemia compared to non dyslipidemic diabetics. The study highlights the fact that in diabetics, oxidatively modified proteins like LDL and albumin may increase with hyperglycemia even before dyslipidemia sets in. Hence, ox LDL and sd LDL may be included in the battery of extended lipid profile to monitor cardiovascular complications in diabetes.

Assessment of lipid profile and some risk factors of atherosclerosis in children whose parents had early onset coronary artery disease.

The objective of our study was to analyze the lipid profile and some risk factors of atherosclerosis such as oxidized-low density lipoprotein (ox-LDL), small dense LDL (sd LDL) in the offspring of patients with premature coronary heart disease (CHD). Children whose parents had early onset CHD were matched with age and sex pairs. Study and controls were analyzed for lipid levels, apolipoproteins (Apo- A,B,E), ox-LDL, sd LDL and lipoprotein (a) [Lp(a)]. The data were evaluated with SPSS using "Student t and Mann-Whitney U" tests. The study group children (n: 43) had higher LDL, Lp(a) and ox-LDL levels, ratios of TC/HDL, Apo-B/A, LDL/HDL and ox-LDL/HDL (p<0.05) than control group. These findings suggest that dyslipidemia and increased LDL, Lp(a) and ox-LDL levels are common in the offspring of patients with early onset CHD and account largely for their familial predisposition for CHD.

Advanced Atherogenic Index for the Assessment of Consolidated Lipid Risk in Premature Coronary Artery Disease Patients in India.

Introduction:The high prevalence, severity, and prematurity of coronary artery disease (CAD) in the Indian population cannot be completely explained by the conventional lipid parameters and the existing lipid indices.Aims and Objectives:To calculate newly defined advanced atherogenic index (AAI) in premature CAD patients and compare it between cases and controls and Correlate its values with the existing indices.Material and Methods:One hundred and twenty premature CAD patients and an equal number of age and sex matched healthy individuals were included in this study. Lipid profile and nonconventional lipid parameters like oxidized Low density lipoprotein (OX LDL), small dense LDL (SD LDL), lipoprotein (a) apolipoprotein B (Apo B), and apolipoprotein A1 (Apo A1) were estimated and their values were used to define AAI and existing lipid indices like AI, lipid tetrad index (LTI) and lipid pentad index (LPI).Results:The mean age of cases and controls was 37.29 + 4.50 and 36.13 + 3.53 years, respectively. The value of AAI was highly significant in cases (3461.22 ± 45.20) as compared to controls (305.84 ± 21.80). AAI has shown better statistical significance and correlation (P < 0.0001, r = 0.737) as compared to the earlier indices such as AI (P < 0.01, r = 0.52), LTI (P < 0.001, r = 0.677) and LPI (P < 0.001, r = 0.622) in premature CAD. Kolmogorov D statistic and cumulative distribution function plot has shown that AAI can discriminate cases and controls more accurately as compared to the earlier indices.Conclusion:Statistically AAI appears to be a better marker of consolidated lipid risk in premature CAD patients as compared to the earlier indices.

A Study of the Extended Lipid Profile including Oxidized LDL, Small Dense LDL, Lipoprotein (a) and Apolipoproteins in the Assessment of Cardiovascular Risk in Hypothyroid Patients.

Hypothyroidism is one of the most common metabolic disorders associated with dyslipidemia which poses a higher risk of Coronary Artery Disease (CAD) in such patients. Biochemical markers which can pick up the risk promptly are becoming imperative now-a-days and thus the assessment beyond the conventional lipid profile is the need of the hour. To assess the association of non-conventional lipid parameters like small dense Low Density Lipoprotein (sd LDL), oxidized Low Density Lipoprotein (ox LDL), Apolipoprotein A (Apo A1), Apolipoprotein B (Apo B) and Lipoprotein (a) {Lp(a)} in hypothyroid patients and compare their values with the conventional lipid parameters such as Total Cholesterol (TC), Triglyceride (TG), Low-Density Lipoprotein Cholesterol (LDL-C) and High-Density Lipoprotein Cholesterol (HDL-C). One hundred and thirty clinically proven patients of hypothyroidism aged 20-60 years and equal number of age and gender matched healthy individuals were included in this case control study. Serum sd LDL, ox LDL, Apo A1, Apo B, Lp (a), lipid profile, Thyroid Stimulating Hormone (TSH), Free Triiodothyronine (FT3) and Free Tetraiodothyronine (FT4) levels were measured in both the groups. The data was recorded and analysed on SPSS system. The results of cases and controls were compared by student t-test and one-way ANOVA. All the parameters were correlated with TSH by Pearson's correlation. We found significantly high levels of sd LDL, ox LDL, Apo B, Lp (a), TC, TG, LDL-C in cases as compared to the controls. Ox LDL has shown maximum correlation with serum TSH (p<0.0001, r=0.801) followed by sd LDL (p<0.0001, r=0.792), Apo B (p<0.001, r=0.783) and LDL-C (p<0.001, r=0.741). Moreover, ox LDL and sd LDL were found to be increased in normolipidemic hypothyroid patients thereby giving a strong supportive evidence that estimation of these parameters can become fundamental in prompt identification of the high risk patients of CAD in hypothyroid population. Non-conventional lipid parameters appear to be better markers for the assessment of cardiovascular risk in hypothyroidism and might help in the designing of the effective treatment protocols and areas of intervention by the clinicians as well as researchers.

Small dense LDL and its Association with Hypertension: a Case-Control Study

Hypertension is one of the most common diseases affecting humans throughout the world. The commonest variety of hypertension is benign essential hypertension. Cardiovascular risk is more in hypertensive patients as their lipid profile is more atherogenic than normotensive subjects. Traditionally, estimation of total serum cholesterol and LDL-C are used as an indicator of atherogenicity. But subjects may develop hypertension and CHD with normal levels of LDL cholesterol. So assessment of LDL cholesterol concentration may not entirely reflect its atherogenic potential. Because LDL-C is not a single entity rather it consists of seven distinct subclasses of different particle size. The size of the LDL particle is inversely correlated to their atherogenicity. Smaller LDL particles are more atherogenic despite their less cholesterol content than the larger more buoyant LDL particles containing more cholesterol. Therefore individuals having smaller LDL particles are more atherogenic and more at risk to develop hypertension inspite of even normal LDL cholesterol concentration. So measurement of small dense LDL particle is more important than any other lipid measure. With this aim 122 subjects were included in this study, among them 82 were diagnosed cases of essential hypertension with the mean age of 42.56±9.98 years and 40 were healthy controls. Serum apo-B was measured in all study subjects. The amount of apoB is almost similar in every LDL subtypes but the amount of cholesterol increases with the increasing particle size. So the ratio of cholesterol to apo-B decreases as the particle size decreases, thus LDL cholesterol / apo-B £ 1 indicates the presence of atherogenic small dense LDL. So the prevalence of small dense LDL was evaluated by calculating the ratio of LDL-C/apo B. The ratio was significantly lower in hypertensive cases (0.093±0.18) compared to controls, indicating presence of sd LDL in hypertensive patients. When the risk ratio was calculated, the patients having small dense LDL in their plasma were found to have 2.87 times more risk for developing CVD then the persons who doesn't have small dense LDL in their plasma. DOI: http://dx.doi.org/10.3329/bjmb.v5i1.13427 Bangladesh J Med Biochem 2012; 5(1): 20-23

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.

THYROID DYSFUNCTION

Objectives: Studies on relation between serum lipids and thyroid dysfunction are numerous but, on the whole, desultory and inconclusive. The aim of this study was to investigate the concentration of serum triglyceride, cholesterol and cholesterol profile in Sudanese patient with thyroid dysfunction. Design: A case control study. Period: April 2008 to June 2009. Setting: Khartoum, Omdurman and Ibrahim Malik teaching Hospital, Khartoum State. Material and Methods: 200 Sudanese patients with thyroid dysfunction (hypothyroidism 100, hyperthyroidism 100) was compared with 100 healthy subjects as control group . Serum samples was taken and cholesterol, triglyceride, LDL and HDL levels were analyzed using colorimetric methods. Results: The mean ±SD serum triglyceride, total cholesterol, HDL and LDL in normal case respectively were 63.3±8.5, 163±6, mg/dl 44.3±3.7 mg/dl, 78.8±8 mg/dl. Among hypothyroidism, the mean ±SD serum total cholesterol, LDL, HDL respectively were 213.9±31.8 mg/dl, 38.5±3.5 mg/dl, 123.8±27.4 mg/dl and also among hyperthyroidism the mean ±SD serum triglyceride, total cholesterol, HDL and LDL respectively were 55.2±6.1mg/dl,152±11.5 mg/dl, 40.7±1.3 mg/dl and 76.1±9.7 mg/dl. Serum level of triglyceride, total cholesterol, and LDL is significantly elevated in hypothyroidism patients when compared with their control group (P&lt;0.05). these changes in lipids profile among hypothyrodism patients are reversed upon thyroxine (T4) replacement therapy(p &lt; 0.05). Conclusions: This study conclude that, the hypothyroidism causes significant increases of serum triglyceride, total Cholestrol, and LDL, with slight decreases in HDL level. In contrast thyroid replacement therapy reversed these changes.

Measurement of lipoprotein particle sizes using dynamic light scattering

A simple method for the measurement of LDL particle sizes is needed in clinical laboratories because a predominance of small, dense LDL (sd LDL) has been associated with coronary heart disease. We applied dynamic light scattering (DLS) to measure lipoprotein particle sizes, with special reference to sd LDL. Human serum lipoproteins isolated by a combination of ultracentrifugation and gel chromatography, or by sequential ultracentrifugation, were measured for particle size using DLS. The sizes of polystyrene beads, with diameters of 21 and 28 nm according to the manufacturer, were determined by DLS as 19.3 +/- 1.0 nm (mean +/- SD, n = 11) and 25.5 +/- 1.0 nm, respectively. The coefficients of variation for the 21 and 28 nm beads were 5.1% and 3.8% (within-run, n = 11), and 2.9% and 6.2% (between-run, n = 3), respectively. The lipoprotein sizes determined by DLS for lipoprotein fractions isolated by chromatography were consistent with the elution profile. Whole serum, four isolated lipoprotein fractions (CM + VLDL + IDL, large LDL, sd LDL and HDL) and a non-lipoprotein fraction isolated by sequential ultracentrifugation were determined by DLS to be 13.1 +/- 7.5, 37.0 +/- 5.2, 21.5 +/- 0.8, 20.3 +/- 1.1, 8.6 +/- 1.5 and 8.8 +/- 2.0 nm, respectively. The proposed DLS method can differentiate the sizes of isolated lipoprotein particles, including large LDL and sd LDL, and might be used in clinical laboratories in combination with convenient lipoprotein separation.

Beneficial effects of atorvastatin on sd LDL and LDL phenotype B in statin-naive patients and patients previously treated with simvastatin or pravastatin

Background The presence of increased levels of small dense (sd) LDL (phenotype B) is associated with a substantial increase of cardiovascular disease risk. Since lowering of plasma low-density lipoprotein-cholesterol (LDL-C) by statins involves an up-regulation of the LDL receptor, we questioned whether LDL lowering by atorvastatin affects different LDL subfractions equally. Methods Fifty-four hypercholesterolemic patients, requiring treatment for prevention of coronary heart disease received atorvastatin (10, 20 or 40 mg/day), either as initial therapy ( n=33), or as replacement therapy ( n=21) for pravastatin or simvastatin (both at 40 mg/day). In addition to plasma lipid measurements, cholesterol LDL subfractions were separated and analysed before and after 3 months of treatment. Results In addition to the expected LDL-C decrease (−34%; p<0.0001), a major reduction in sd LDL occurred after atorvastatin therapy (−38.2%; p<0.0001). Interestingly, sd LDL decreased as much in patients previously treated with other statins (−36%; p<0.002). A close correlation ( r=0.89, p<0.001) was found between reduction of sd LDL and that of LDL-C, in patients with phenotype B. Although high-density lipoprotein-cholesterol (HDL-C) was not affected by atorvastatin treatment, plasma triglycerides decreased by 27.4% ( p<0.0001). Only a weak correlation ( r=0.35, p<0.01) was found between the reduction of plasma triglycerides and the decrease of sd LDL after atorvastatin treatment. Conclusion These results show that the reduction of LDL-C by atorvastatin largely reflects a lowering of sd LDL. Our data also suggest that triglyceride lowering plays only a partial role in sd LDL reduction.

A novel and simple method for quantification of small, dense LDL

A preponderance of small, dense (sd) LDL is strongly associated with the development of coronary heart disease, but the method for the measurement of sd LDL is too laborious for clinical use. We report a simple method for the quantification of sd LDL that is applicable to an autoanalyzer. This method consists of two steps: first, to precipitate the lipoprotein of density (d) <1.044 g/ml using heparin-magnesium; and second, to measure LDL-cholesterol in the supernatant by the homogeneous method or apolipoprotein B (apoB) by an immunoturbidometric assay. The cholesterol and apoB values obtained by the precipitation method (45 +/- 26 and 33 +/- 20 mg/dl, respectively) were similar to those obtained in the lipoprotein (d = 1.044-1.063) separated by ultracentrifugation (42 +/- 22 and 31 +/- 17 mg/dl, respectively), and there was an excellent correlation between the two methods for sd LDL-cholesterol (y = 1.05X + 1, r = 0.88, n = 69) and apoB (y = 1.07X, r = 0.90). Sd LDL values had a significant inverse correlation with LDL size. A high correlation was found between sd LDL-cholesterol and apoB values (r = 0.94). Sd LDL value was related to triglyceride, apoB, and LDL-cholesterol, but not to the buoyant LDL level. These results suggest that this precipitation method is a simple and rapid method for the measurement of sd LDL concentration.