Hypertriglyceridemia is a Major Factor Associated With Elevated Levels of Small Dense LDL Cholesterol in Patients With Metabolic Syndrome

BACKGROUND: We aimed to determine the major contributing component of metabolic syndrome (MetS) that results in an elevated small dense LDL cholesterol (sdLDL-C) concentration and sdLDL-C/LDL-C ratio. METHODS: Four hundred and forty-seven subjects (225 men; 222 women) with MetS were randomly selected from the Korean Metabolic Syndrome Research Initiatives-Seoul cohort study. Age- and sex-matched healthy controls (181 men; 179 women) were also randomly selected from the same cohort. RESULTS: A comparison of the median values of the sdLDL-C concentration between subgroups, divided according to whether subjects met or did not meet the criteria for each MetS component in patients with MetS, revealed a significant difference in the sdLDL-C concentration only between subgroups divided according to whether subjects met or did not meet the triglyceride (TG) criteria (P<0.05 for each gender). The TG level showed a good correlation with sdLDL-C concentration (correlation coefficients [r]=0.543 for men; 0.653 for women) and the sdLDL-C/LDL-C ratio (r=0.789 for men; 0.745 for women). Multiple linear regression analyses conducted for the MetS group concordantly identified TG as one of the most significant contributors to sdLDL-C concentration (beta=0.1747+/-0.0105, P<0.0001) and the sdLDL-C/LDL-C ratio (beta=6.9518+/-0.3011, P<0.0001). CONCLUSIONS: Among five MetS components, only the abnormal TG level was a differentiating factor for sdLDL-C concentration and sdLDL-C/LDL-C ratio. These results were reproducible in both genders, with or without MetS.

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.

LDL pequeña y densa en adultos y su relación con factores de riesgo cardiovascular tradicionales

Objetivos: Establecer la presencia de lipoproteína de baja densidad pequeña y densa (LDLpd) en suero y su relación con factores de riesgo cardiovascular tradicionales en adultos. Métodos: Se estudiaron 78 mujeres y 73 hombres con promedio de edad de 39,9±14,9 años (rango: 20-84 años), los cuales asistieron a un centro de salud del Edo. Carabobo, Venezuela. Se registró hábito tabáquico, presión arterial y medidas antropométricas. Se obtuvo muestra de sangre en ayunas en la que se cuantificó colesterol total y fraccionado y triglicéridos mediante métodos enzimáticos-colorimétricos y se detectó LDLpd a través de electroforesis en gel de poliacrilamida en gradiente. El consumo de alcohol y su patrón de ingesta se registró mediante el Test de Identificación de Desórdenes del Uso del Alcohol (AUDIT). Resultados: Se detectó LDLpd en 45,7% de los individuos, siendo más frecuente en las mujeres que en los hombres (57,7% vs. 32,9%). La presencia de LDLpd se asoció significativamente con el aumento de la edad, índice de masa corporal, circunferencia de cintura, colesterol total, LDL colesterol y triglicéridos así como con la disminución de HDL colesterol. La presencia de LDLpd fue más frecuente entre los fumadores, hipertensos y aquellos individuos que consumieron alcohol en mayor cantidad y frecuencia. La presencia de LDLpd en suero fue predicha significativamente por la edad y los niveles de triglicéridos y HDL colesterol. Conclusiones: En este estudio, la presencia de LDLpd en suero fue frecuente en los individuos estudiados y se encontró relacionada con los factores de riesgo cardiovascular tradicionales evaluados.

Objectives: To establish the presence of small dense Low Density Lipoproteins (sdLDL) in serum and possible relation with traditional cardiovascular risk factors in adult individuals. Methods:We studied 78 women and 73 men with a mean age of 39.9 ± 14.9 years (range: 20-84 years) who attended to a health center of Edo. Carabobo, Venezuela. Measures were recorded smoking habit, blood pressure and anthropometric . After informed consent, patients were clinically evaluated and. Total and fractionated cholesterol and triglycerides were determined in serum by enzymatic-colorimetric methods. The presence of serum sdLDL was detected by polyacrylamide gradient gel electrophoresis. Alcohol consumption and drinking pattern were recorded by Alcohol Use Disorders Identification Test (AUDIT). Results: sdLDL was detected in 45.7% of individuals, being more prevalent in women than in men (57.7% vs. 32.9%). The presence of sdLDL in serum was significantly associated with the increasing age, body mass index, waist circumference, total cholesterol, LDL cholesterol, triglycerides and the decrease of HDL cholesterol. The presence of sdLDL was more common among smokers, hypertensives and those individuals who consumed alcohol in more quantity and frequency. Age, triglyceride and HDL cholesterol significantly predicted the presence of sdLDL. Conclusions: In this study, the presence of serum sdLDL was common in study subjects and related to traditional cardiovascular risk factors.

Effect of Omega-3 Fatty Acids on Low Density Lipoprotein Subfraction, Adiponectin and Apolipoprotein B in Type 2 Diabetic Patients

BACKGROUND: Omega-3 fatty acids derived from fish oil have been reported to exert a beneficial effect on reducing cardiovascular disease. Reports about their mechanism have generated several interesting findings, including a change in small dense low density lipoprotein (sdLDL) cholesterol proportion, adiponectin, and apolipoprotein B (apoB), in addition to changes in the lipid profile. The principal objective of our study was to evaluate the effects of omega-3 fatty acids on plasma sdLDL, adiponectin, apoB100, and B48 in type 2 diabetic patients with hypertriglyceridemia. METHODS: We randomized 28 type 2 diabetic patients in a placebo-controlled, double-blind trial to receive either omega-3 fatty acids or placebo, both administered at a dose of 4 g daily for 12 weeks. LDL subfractions prior to and after treatment were separated via low-speed ultracentrifugation and analyzed via immunoelectrophoresis. Adiponectin, apoB100, and B48 levels were measured using an ELISA kit. RESULTS: sdLDL proportions were reduced in the omega-3 fatty acids group by 11% after 12 weeks of treatment (n = 17, P = 0.001), and were reduced by 4% in the control group (n = 11, P = 0.096). The patients receiving the omega-3 fatty acids evidenced a significant reduction in the levels of triglyceride (P = 0.001), apoB100, and B48 after 12 weeks (P = 0.038 and P = 0.009, respectively) relative to the baseline. Omega-3 fatty acids supplementation increased fasting blood glucose (P = 0.011), but the levels of HbA1c in each group did not change to a statistically significance degree. The adiponectin value was not reduced in the omega-3 fatty acids group (P = 0.133); by way of contrast, the placebo group evidenced a significant reduction in adiponectin value after 12 weeks (P = 0.002). CONCLUSION: Omega-3 fatty acid treatment proved effective in the reduction of atherogenic sdLDL and apoB in type 2 diabetic patients (Clinical trials reg. no. NCT 00758927, clinicaltrials.gov).

A Higher Burden of Small Low-density Lipoprotein Particles is Associated with Profound Changes in the Free Androgen Index in Male Adolescents

From a young age, males are at higher cardiovascular risk than females. Dyslipidemia, including a higher burden related to small low-density lipoproteins (LDL), plays an important role in precipitating atherosclerosis in both males and females. We investigated sex differences in atherogenic lipoprotein burden and the independent predictors of LDL particle size in children and adolescents. We measured the concentrations of total testosterone, sex hormone-binding globulin, estradiol, total cholesterol, triglyceride, LDL cholesterol, HDL cholesterol, and LDL particle size in 135 children and adolescents (67 boys, 68 girls). The free androgen index was significantly and negatively correlated with LDL particle size (r = -0.273, P = 0.026) in boys, but estrogen and LDL particle size were not related. In a stepwise multiple regression analysis adjusted for body mass index, age, and homeostasis model assessment for insulin resistance, free androgen index was still an independent predictor of LDL particle size in boys (R2 = 0.075, P = 0.026). The prominent decrease in LDL particle size along with increased testosterone concentrations in males might explain why they are more likely to display atherogenic dyslipidemia from adolescence.

The Relationship between the Leptin Concentration and the Small Dense Low Density Lipoprotein Cholesterol Concentration in Korean Type 2 Diabetic Patients / 대한내분비학회지

BACKGROUND: Leptin has been suggested as a possible cause of atherosclerotic disease. The small dense low-density lipoprotein cholesterol (LDL-C) has also been regarded as a new surrogate marker in atherosclerotic disease. The aim of this study was to evaluate the relationship between the leptin concentration and the small dense LDL-C concentration in Korean type 2 diabetic patients. METHODS: One hundred-ninety one type 2 diabetic patients, who did not use any medication that could affect the concentration of lipid such as statin, fibrate, thiazolidinediones and corticosteroid, were enrolled in this study. We analyzed the relationship between leptin, the small dense LDL-C and the other metabolic parameters. RESULTS: The small dense LDL-C concentrations were higher in the group with the highest tertile of the leptin value, both in males and females than those patients in the group with the lowest tertile of the leptin value. The small dense LDL-C concentrations were also higher in the group with the highest tertile of leptin divided by the BMI value both in males and females than those patients in the group with the lowest tertile of the leptin value. The leptin concentration was positively correlated with the small dense LDL-C, total cholesterol, triglyceride, LDL-C, insulin and HOMAIR values after adjusting for age, gender and BMI. CONCLUSION: The association between leptin and small dense LDL-C could be a factor that explains the association between leptin and cardiovascular disease.

The Relationship between the Leptin Concentration and the Small Dense Low Density Lipoprotein Cholesterol Concentration in Korean Type 2 Diabetic Patients / 대한내분비학회지

BACKGROUND: Leptin has been suggested as a possible cause of atherosclerotic disease. The small dense low-density lipoprotein cholesterol (LDL-C) has also been regarded as a new surrogate marker in atherosclerotic disease. The aim of this study was to evaluate the relationship between the leptin concentration and the small dense LDL-C concentration in Korean type 2 diabetic patients. METHODS: One hundred-ninety one type 2 diabetic patients, who did not use any medication that could affect the concentration of lipid such as statin, fibrate, thiazolidinediones and corticosteroid, were enrolled in this study. We analyzed the relationship between leptin, the small dense LDL-C and the other metabolic parameters. RESULTS: The small dense LDL-C concentrations were higher in the group with the highest tertile of the leptin value, both in males and females than those patients in the group with the lowest tertile of the leptin value. The small dense LDL-C concentrations were also higher in the group with the highest tertile of leptin divided by the BMI value both in males and females than those patients in the group with the lowest tertile of the leptin value. The leptin concentration was positively correlated with the small dense LDL-C, total cholesterol, triglyceride, LDL-C, insulin and HOMAIR values after adjusting for age, gender and BMI. CONCLUSION: The association between leptin and small dense LDL-C could be a factor that explains the association between leptin and cardiovascular disease.

Significance of Small Dense Low-Density Lipoprotein as a Risk Factor for Coronary Artery Disease and Acute Coronary Syndrome

Small dense LDL (sd-LDL) has recently emerged as an important coronary artery disease (CAD) risk factor. This study was performed to investigate how LDL particle size is related to CAD and acute coronary syndrome (ACS). Blood samples were collected from 504 patients that underwent coronary angiography to evaluate chest pain. The LDL particle size of these samples was measured. The mean LDL particle size was smaller in patients with angiographically proven CAD than in the controls (26.41+/-0.95 vs 26.73+/-0.64nm, p < 0.001), and was negatively correlated with the Framingham risk score (r=-0.121, p=0.007). Patients with more extensive CAD had smaller LDL particles. LDL particle size was also smaller in patients with acute coronary syndrome as compared to non-ACS patients (26.09+/-1.42 vs 26.54+/-0.63nm, p=0.011). These results suggest that sd-LDL is independently associated with the incidence and extent of CAD, and can be a risk factor for the development of ACS in the Korean population.