Low-density Lipoprotein Pattern Research Articles

Abstract 13422: Long Term Association of Low Density Lipoprotein Patterns With Coronary Artery Calcium and Atherosclerotic Cardiovascular Disease Events: Insights From HeartSCORE Study

Introduction: Low-density lipoprotein (LDL) cholesterol, a factor in progression of atherosclerotic cardiovascular disease (CVD), consists of sub-fractions with different sizes and densities in three patterns (A (large buoyant), B (small dense), AB (intermediate pattern). We examined the associations of LDL patterns with subclinical ASCVD and future events. Methods: Participants from the Heart Strategies Concentrating on Risk Evaluation (HeartSCORE) study were assessed for baseline lipid levels and LDL sub-fraction types by an ultracentrifugation method (vertical auto profile). Electron beam CT scans were obtained in a subset of individuals and coronary artery calcium (CAC) scores were calculated (Agatston method). Adjusted odds ratios and hazard ratios (95% CI) were calculated using logistic regression and Cox regression, respectively, to estimate the independent association between LDL sub-fractions and both; CAC and ASCVD events (MI, ischemic stroke, death), respectively. Results: Among 1884 eligible participants (mean [SD] age; 59[7.5]y, 65.8% women, 37.9% black), mean HDL-c, LDL-c and Triglycerides were 142.2[36.0]mg/dL, 58.2[14.9]mg/dL and 111.2[47.7]mmHg, respectively. Sub-fractions of LDL pattern A, B and AB were observed in 761(40%), 507(26.9%) and 616(32.7%) individuals. Over a follow up of ~16y, patterns B(1.98[1.22-3.21) and AB (1.54[1.00-2.38)] were independently associated with incident risk of CVD events (vs pattern A). When stratified by race and gender, pattern AB showed independent risk of incident CVD events and CAC presence among blacks and males (Table) . Conclusions: In this biracial cohort of middle-aged adults, LDL sub-fraction patterns B and AB showed a significantly higher risk of long-term CVD events. Pattern AB was also associated with positive CAC in blacks and males. Further studies are needed to investigate LDL patterns in CVD risk profiling based on race and gender.

A Case–Control Study to Evaluate Serum Lipoprotein Levels and Other Biomarkers of Cardiovascular Disease in Patients With Psoriasis

Background: Studies investigating lipid abnormalities associated with psoriasis have reported conflicting results. The purpose of this study is to evaluate differences in serum lipoprotein levels among patients with psoriasis compared to controls via the use of the Vertical Auto Profile (VAP) test, which directly measures the cholesterol concentrations of all 5 lipoprotein classes and their subclasses. We also assess other cardiovascular biomarkers, including highly sensitive C-reactive protein (hs-CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2), and homocysteine. Methods: In this 6-year case–control study, 210 patients (110 patients with psoriasis and 100 controls) elected to participate in VAP testing between November 2009 and April 2016 at The George Washington Medical Faculty Associates dermatology clinic. All psoriatic cases were age-, sex-, and body mass index–matched to control patients. Data were analyzed in June 2016. We evaluated cardiovascular biomarkers in patients with psoriasis versus control patients and whether an association exists between the presence of psoriasis and the level of cardiovascular dysfunction. Results: Compared to the control group, patients with psoriasis had significantly lower high-density lipoprotein (HDL) ( P = .007), HDL2 ( P = .013), and HDL3 cholesterol ( P = .015) as well as higher low-density lipoprotein (LDL) pattern B ( P= .032), LDL3 ( P = .030), and LDL4 cholesterol ( P = .003). Patients with psoriasis also had lower apolipoprotein A1 ( P = .011), lower Lp-PLA2 ( P = .037), and higher hs-CRP ( P = .048). Conclusion: Our findings suggest an increased risk of cardiovascular biomarker dysfunction in patients with psoriasis compared to their matched controls. Serum biomarkers such as high LDL pattern B, LDL3, and LDL4 as well as lower HDL2, HDL3, and total HDL were found to have a higher association with psoriatic disease.

Impact of the modified Atkins diet on cardiovascular health in adults with epilepsy

AimThe current study investigated biochemical and vascular markers of cardiovascular health in adult patients with epilepsy treated with long-term (greater than 1year) ketogenic diet therapy compared with controls. MethodAnthropometric measures, serum fasting lipid panel, apolipoproteins A-1 and B, lipoprotein sub-fractions as well as common carotid intima-media thickness (cIMT), and plaque presence were assessed in 20 adult patients with epilepsy on a modified Atkins diet (MAD) for >1year started as an adult compared with 21 adult patients with epilepsy naïve to diet therapy. ResultsPatients treated with MAD had significantly lower weight, body mass index, waist and hip circumference, percent body fat, and serum triglyceride levels when compared with control patients. In contrast, they had significantly higher serum levels of small low-density-lipoprotein (LDL) particles and were significantly more likely to have LDL pattern B in which small LDL particles predominate when compared with controls. However, there was no significant difference in cIMT or plaque presence between groups. ConclusionOur results provide clinical evidence demonstrating the cardiovascular safety of a high-fat, low-carbohydrate diet used in adults with epilepsy for at least 12months. It also highlights potential markers of cardiovascular risk – small dense LDL particles – that should be closely monitored in adults treated with diet therapy long-term.

Association of low-density lipoprotein pattern with mortality after myocardial infarction: Insights from the TRIUMPH study

Studies of incident coronary heart disease risk within low-density lipoprotein (LDL) subclass (small, dense vs large, buoyant) have shown mixed results. No prospective cohort study has examined the association of small, dense, or large, buoyant LDL with mortality after myocardial infarction (MI). The objective of the study was to examine association of LDL pattern after MI and death. In 2476 patients hospitalized for MI, LDL pattern (A [large, buoyant], A/B [mixed], and B [small, dense]) was established by ultracentrifugation using Vertical Auto Profile. Using time-to-event analysis, we examined the association with 5-year mortality within LDL patterns, after adjusting for important patient and treatment characteristics. We additionally adjusted for LDL cholesterol (LDL-C) and triglyceride levels and used directly measured LDL-C and non-high-density lipoprotein cholesterol as exposures. Patterns A, A/B, and B were present in 39%, 28%, and 33% of patients, respectively, with incident rates (per 1000 patient-years) of 50, 34, and 24 for all-cause and 24, 19, and 10 for CV mortality. The hazard ratios (95% confidence interval) with LDL patterns A/B and B compared with pattern A were 0.77 (0.61, 0.99) and 0.67 (0.51, 0.88) for all-cause, 0.94 (0.67, 1.33) and 0.69 (0.46, 1.03) for cardiovascular, and 0.64 (0.45, 0.91) and 0.65 (0.45, 0.93) for noncardiovascular mortalities, respectively. Results were similar when further adjusted for LDL-C and triglycerides, or with LDL-C and non-high-density lipoprotein cholesterol as exposures. Compared with LDL pattern A, pattern B was significantly associated with reduced all-cause and non-CV mortalities with a trend for lower CV mortality after MI, independent of LDL-C and triglycerides.

Efficacy of a telephone-based medical nutrition program on blood lipid and lipoprotein metabolism: Results of Our Healthy Heart.

Derangements in blood lipid and lipoprotein metabolism are one of the leading causes of coronary heart disease (CHD). Therapeutic lifestyle changes such as diet and exercise are often prescribed to improve blood lipid and lipoprotein characteristics, but the efficacy of a telephone-based health coaching program has not been thoroughly explored. Our purpose was to examine effects of the Our Healthy Heart (OHH) Program on blood lipid and lipoprotein characteristics of individuals with mixed dyslipidaemia. Cholesterol content of serum very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density (HDL) subfractions and apolipoprotein concentrations were measured by vertical-density ultracentrifugation (Vertical Auto Profile (VAP)) from 1522 individuals with mixed dyslipidaemia (age 18-99 years, body mass index (BMI) 25-40, 62.7% female). Telephone-based health coaching (OHH, n = 722) or standard care (Control, n = 800) was provided for six months followed by VAP to evaluate changes in lipid and lipoprotein concentrations. Controls were obtained from individuals with similar blood lipid/lipoprotein characteristics who did not participate in the OHH Program. Coaches collected baseline self-reported data on anthropometrics, food intake and exercise. Participants in the OHH group were then prescribed a hypocaloric 500 kcal/day caloric deficit with encouragement to participate in physical activity. A two-way ANOVA was used to examine differences between groups over time, with results presented as means ± standard deviation. Health coaching significantly decreased serum concentrations of apoB100 (104.5 ± 25.8-94.3 ± 24.8 mg/dL), shifted LDL pattern size from B to A or A/B in over 60% of the OHH group and decreased cholesterol content of all VLDL subfractions (P < 0.05) compared to the control. Telephone-based health coaching recommendations to reduce dietary energy intake and increase physical activity produced significant improvements in cholesterol content of atherogenic lipoproteins, which are known to increase CHD risk.

The metabolic inter‐relationships between changes in waist circumference, triglycerides, insulin sensitivity and small, dense low‐density lipoprotein particles with acute weight loss in clinically obese children and adolescents

Small, dense low-density lipoprotein (LDL) particles are highly atherogenic and strongly associated with obesity-related dyslipidemia. The metabolic inter-relationships between weight loss induced changes in waist circumference, triglycerides, insulin sensitivity and small-dense LDL particles in clinically obese children and adolescents have not been studied. Seventy-five clinically obese boys and girls (standardized body mass index 3.07 ± 0.59, aged 8-18 years) were recruited. Anthropometric, body composition and cardiometabolic risk factors were measured pre- and post-weight loss. There were highly significant reductions in anthropometric, body composition and cardiometabolic risk factors. Triglyceride change was positively correlated with LDL peak particle density and percentage LDL pattern B changes (relative abundance of small, dense LDL particles). Multiple regression analyses showed that changes in triglyceride concentration accounted for between 24 and 18% of the variance in LDL peak particle density and percentage LDL pattern B change, respectively. Changes in waist circumference and insulin sensitivity did not predict these changes in LDL characteristics. Acute and highly significant weight loss significantly decreased LDL peak particle density and percentage LDL pattern B. The change in triglycerides was a strong predictor of LDL peak particle density and percentage LDL pattern B change.

Abstract 18939: Impact of LDL Pattern on Risk for CHD in the Framingham Offspring Population

Introduction : Low-density lipoprotein (LDL) particles that are small and dense are characteristic of pattern B. It has been assumed that such particles are more atherogenic than larger, more buoyant particles indicative of LDL pattern A. Additionally, there is evidence from observational studies to support LDL pattern B as an emerging risk factor for coronary heart disease (CHD) with the incidence of CHD increasing as the proportion of type B to type A LDL particles increases. Hypothesis: In participants in the Framingham Offspring Cohort Study (FOCS), LDL pattern B is a significant and independent risk factor for incident CHD (inclusive of coronary death, myocardial infarction, coronary insufficiency, and angina pectoris) and hard CHD (CHD endpoints exclusive of angina pectoris). Methods : Vertical auto profile measurements were performed on 819 men and women on no lipid-modifying therapy as part of an exploratory analysis of the FOCS. The relationship between increasing LDL pattern type (A, A/B, and B) and 12-year risk for CHD and hard CHD was quantified using multivariable Cox proportional hazard regression for two models adjusted for known Framingham risk factors (model 1 adjusts for age, sex, systolic blood pressure and use of antihypertensives, prevalent diabetes, and smoking; model 2 adjusts for model 1 risk factors, HDL-C, and total cholesterol). Results: LDL pattern B is a statistically significant ( p &lt; 0.05 ) independent risk factor for 12-year incident CHD with hazard ratios of approximately 1.4 in models 1 and 2. For incident hard CHD, LDL pattern B is a more significant risk factor with hazard ratios greater than two and p &lt; 0.005 across both models. There was no effect modification by sex ( p &gt; 0.7 ). Conclusions: In this exploratory analysis, LDL pattern B is an independent risk factor for CHD and hard CHD after controlling for known Framingham risk factors in men and women on no lipid-lowering therapy.

Reversal of Small, Dense LDL Subclass Phenotype by Weight Loss Is Associated With Impaired Fat Oxidation

Adiposity is more prevalent among individuals with a predominance of small, dense low-density lipoprotein (LDL) (pattern B) particles than among those with larger LDL (pattern A). We tested for differences in resting energy expenditure (REE) and respiratory quotient (RQ) in overweight men with pattern A (n = 36) or pattern B (n = 60). Men consumed a standardized isoenergetic diet for 3 weeks after which a ~9kg weight loss was induced by caloric deficit for 9 weeks, followed by 4 weeks of weight stabilization. REE and RQ were measured by indirect calorimetry before and after weight loss. Results were analyzed separately in pattern B men who converted to pattern A (B→A; n = 35) and those who did not (B→B; n = 25). At baseline, B→B men had higher trunk fat, triacylglycerol (TG) and insulin concentrations, homeostasis model assessment of insulin resistance (HOMA(IR)), and smaller LDL particles compared to B→A men and baseline pattern A men who remained pattern A (A→A; n = 35). REE normalized to fat-free mass did not change after weight loss. RQ decreased in A→A men, increased in B→A men, and did not change significantly in B→B men after weight loss. Calculated fat oxidation rates paralleled the RQ results. Baseline plasma TG concentrations were positively correlated with RQ and inversely correlated with the magnitude of weight loss achieved for a given prescribed energy reduction in the entire study population. Pattern B men who converted to pattern A with weight loss may have an underlying impairment in fat oxidation that predisposes to both dyslipidemia and an impaired ability to achieve weight loss by energy restriction.

Population variations in atherogenic dyslipidemia: A report from the HeartSCORE and IndiaSCORE Studies

Asian Indians and blacks have a higher risk for cardiovascular disease (CVD) events compared to whites. Atherogenic dyslipidemia, comprised of small-dense low-density lipoprotein (LDL), low high-density lipoprotein (HDL) levels, and high triglyceride (TG) levels, constitutes an important risk factor for CVD often seen in the presence of obesity. The contribution of atherogenic dyslipidemia to CVD risk across diverse racial populations is not well established. Our primary aim was to investigate the relationship between race and atherogenic dyslipidemia among whites, blacks, and Asian Indians. A secondary aim was to evaluate the association between obesity and atherogenic dyslipidemia across populations. From community-based sampling, 720 whites and 373 blacks underwent evaluation of CVD risk factors, including fasting lipoproteins. An identical protocol was administered to 205 Asian Indians from Chennai, India. Lipid profiles, including those comprising atherogenic dyslipidemia, were compared among populations. The prevalence of small-dense LDL (pattern B) and of TG/HDL ratio >3 was greatest among Asian Indians and smallest among blacks. Compared to whites, the adjusted odds for Indians having a LDL pattern B was 2.06 (P < .001) and TG/HDL ratio >3 was 9.42 (P < .001). The adjusted odds of having LDL pattern B (odds ratio 0.39, P < 0.001) or TG/HDL ratio >3 (odds ratio 0.41, P < .001) was lower in blacks compared to whites. Among Indians, obesity had a weak association with atherogenic dyslipidemia, in contrast to the strong association among whites. Significant population variations in atherogenic dyslipidemia exist. This may be an important component to explain population differences in cardiovascular risk.

Associations of apolipoprotein E polymorphism with low-density lipoprotein size and subfraction profiles in Arab patients with coronary heart disease

The APOE gene locus has 3 major alleles, E3, E4 and E2, which variably influence coronary heart disease (CHD) risk. Plasma low-density lipoprotein (LDL) profile, another major CHD risk factor, is characterized on the basis of size and density into 2 main patterns: large buoyant LDL and small dense LDL. The latter has also been linked with increased CHD risk. This study investigates associations of specific APOE allelic patterns with LDL size and subfraction profiles in patients with CHD and healthy control subjects. We recruited 2 groups of male subjects: (A) 65 apparently healthy control subjects, median age, 39.0 years (range, 25.0-60.0 years); (B) 50 patients with CHD, median age, 54.0 years (range, 40.0-76.0 years). APOE genotypes were determined by validated polymerase chain reaction-restriction fragment length polymorphism methods, and LDL size and subfractions were assessed by a high-resolution, nongradient polyacrylamide gel electrophoresis technique (LIPOPRINT, Quantimetrix, Redondo Beach, CA). Lipid and other biochemical analyses were done by autoanalyzer techniques. The associations of specific APOE alleles and genotypes with LDL size and subfraction patterns were then assessed. As expected, patients with CHD had a worse atherogenic lipoprotein profile (waist-hip ratio, LDL, uric acid, and apolipoprotein B) than the controls. APOE genotype and allele frequencies were similar for both groups. In either group, median percent large buoyant LDL (pattern A) was greater in controls (51.0% vs 46.5%, P < .001) and percent small dense LDL (pattern B) was greater with CHD (9.0% vs 3.0%, P < .001). The latter also had smaller median particle size (26.5 vs 26.9 nm, P < .001). In controls, percent LDL pattern B was significantly lower with APOE2 than with APO non-E2 (4.0% vs 0.0%, P < .05); in patients with CHD, E2 patients had smaller particle size, and pattern B was significantly lower with non-E2 than with E2 (15.0 vs 8.0, P < .05). With respect to E4, control non-E4 had a smaller median percent LDL pattern B than E4; otherwise, there were no significant findings in relation to APOE type and LDL size and subfractions in both subject groups. These results confirm observations in other populations of increased levels of small dense LDL in patients with CHD. Although the APOE allelic pattern, especially APOE2, could be related to LDL subfraction profiles in control subjects, such associations could not be demonstrated in those with CHD.

Dietary cholesterol provided by eggs and plasma lipoproteins in healthy populations

Extensive research has not clearly established a link between egg consumption and risk for coronary heart disease. The effects of egg intake on plasma lipids and low-density lipoprotein (LDL) atherogenicity in healthy populations need to be addressed. The lack of connection between heart disease and egg intake could partially be explained by the fact that dietary cholesterol increases the concentrations of both circulating LDL and high-density lipoprotein (HDL) cholesterol in those individuals who experience an increase in plasma cholesterol following egg consumption (hyperresponders). It is also important to note that 70% of the population experiences a mild increase or no alterations in plasma cholesterol concentrations when challenged with high amounts of dietary cholesterol (hyporesponders). Egg intake has been shown to promote the formation of large LDL, in addition to shifting individuals from the LDL pattern B to pattern A, which is less atherogenic. Eggs are also good sources of antioxidants known to protect the eye; therefore, increased plasma concentrations of lutein and zeaxanthin in individuals consuming eggs are also of interest, especially in those populations susceptible to developing macular degeneration and eye cataracts. For these reasons, dietary recommendations aimed at restricting egg consumption should not be generalized to include all individuals. We need to acknowledge that diverse healthy populations experience no risk in developing coronary heart disease by increasing their intake of cholesterol but, in contrast, they may have multiple beneficial effects by the inclusion of eggs in their regular diet.

Gemfibrozil Reduces Small Low-Density Lipoprotein More in Normolipemic Subjects Classified as Low-Density Lipoprotein Pattern B Compared With Pattern A

We tested the hypothesis that gemfibrozil has a differential effect on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclass distributions and postprandial lipemia that is different in subjects classified as having LDL subclass pattern A or LDL pattern B who do not have a classic lipid disorder. Forty-three normolipemic subjects were randomized to gemfibrozil (1,200 mg/day) or placebo for 12 weeks. Lipids and lipoproteins were determined by enzymatic methods. The mass concentrations of lipoproteins in plasma were determined by analytic ultracentrifugation and included the S(f) intervals: 20 to 400 (very LDL), 12 to 20 (intermediate-density lipoprotein), 0 to 12 (LDL), and HDL(2) mass (F(1.20) 3.5 to 9.0) and HDL(3) mass (F(1.20) 0 to 3.5). Postprandial measurements of triglycerides and lipoprotein(a) were taken after the patients consumed a 500 kcal/M(2) test meal. Treatment with gemfibrozil, compared with placebo, significantly reduced fasting plasma triglycerides (difference from placebo +/- SE; -50.2 +/- 20.6 mg/dl, p = 0.02), total cholesterol (-16.4 +/- 7.5 mg/dl, p = 0.04), apolipoprotein B (-16.1 +/- 5.5 mg/dl, p = 0.006), very LDL mass of S(f) 20 to 400 (-50.8 +/- 24.1 mg/dl, p = 0.02), S(f) 20 to 60 (-17.5 +/- 8.5 mg/dl, p = 0.05), S(f) 60 to 100 (-16.2 +/- 8.1 mg/dl, p = 0.05), and increased peak S(F) (0.48 +/- 0.27 Svedberg, p = 0.08). Gemfibrozil reduced the postprandial triglyceride level significantly at 3 (p = 0.04) and 4 (p = 0.05) hours after the test meal. A significantly different subclass response to gemfibrozil was observed in those with LDL pattern A versus B. Those with LDL pattern B had a significantly greater reduction in the small LDL mass S(f) 0 to 7 (p = 0.04), specifically regions S(f) 0 to 3 (p = 0.009) and S(f) 3 to 5 (p = 0.009). In conclusion, normolipemic subjects with either predominantly dense or buoyant LDL respond differently to gemfibrozil as determined by the changes in LDL subclass distribution. Thus, treatment with gemfibrozil may have additional antiatherogenic effects in those with LDL pattern B by decreasing small dense LDL that is not apparent in those with pattern A.

Atorvastatin Reduces Remnant Lipoproteins and Small, Dense Low‐Density Lipoproteins Regardless of the Baseline Lipid Pattern

Elevated plasma levels of remnant lipoproteins and small, dense low-density lipoprotein (LDL) particles increase the risk of atherosclerosis. This prospective, placebo-controlled, crossover trial evaluated the effect of atorvastatin on various lipid parameters including remnant lipoproteins and small, dense-LDL cholesterol levels. Forty-five subjects were enrolled in the study. These subjects fell into three distinct lipid patterns: atherogenic dyslipidemia, isolated hypercholesterolemia, and mixed dyslipidemia. Regardless of the baseline lipid profile, atorvastatin (10 mg q x d) reduced levels of remnant lipoproteins by 25%, LDL-cholesterol by 27%, and the three LDL subfractions by 23%-28% (p<0.0001 for all). Combining all patients, atorvastatin did not significantly alter the overall LDL subfraction pattern; however, in the isolated hypercholesterolemia group, the proportion of LDL present as the small, dense fraction increased by 23% (p=0.01) with treatment, whereas it did not change significantly in the other two groups. Overall, atorvastatin reduced triglycerides by 18% and apolipoprotein-B100 by 23% and increased high-density lipoproteins by 6.2% (p<0.001 all). Since atorvastatin is known to reduce the risk for coronary heart disease events and these data suggest that it does not appear to alter the LDL subfraction pattern, it is unclear whether or not the latter is an important risk predictor independent of LDL-cholesterol concentrations. Increased attention should be paid to absolute concentrations of LDL subfraction cholesterol, which may be a more sensitive indicator of coronary heart disease risk than total LDL or an LDL pattern.

Differential effect of two nicotinic acid preparations on low-density lipoprotein subclass distribution in patients classified as low-density lipoprotein pattern A, B, or I

We tested the hypothesis that treatment with nicotinic acid results in a differential blood lipid response in subjects classified as having a low-density lipoprotein (LDL) pattern A or B. One hundred eighty hypercholesterolemic subjects were randomized to placebo (n = 61), immediate-release niacin (3,000 mg/day, n = 59), or extended-release niacin (1,500 mg/day, n = 60) for 14 weeks. Lipids and lipoprotein cholesterol were determined with enzymatic methods. LDL subclass distribution was determined with 2% to 16% polyacrylamide gradient gel electrophoresis. Extended- and immediate-release niacin had significant effects on the decrease of triglycerides, total cholesterol, LDL cholesterol, apoprotein B, lipoprotein(a), and apoprotein A-I and significantly increased high-density lipoprotein cholesterol. The 2 nicotinic acid compounds and doses significantly increased mean LDL peak particle diameter and percent distribution in large LDL I and IIa, with a significant decrease in small LDL IIIa, IIIb, and IVb. In patients with LDL pattern B compared with those with pattern A, extended-release niacin (1,500 mg/day) increased LDL peak particle diameter significantly more and decreased the percent distributions of small LDL IIIa, LDL IIIb, and LDL IVa significantly more. With 3,000 mg/day, immediate-release nicotinic acid in patients with LDL pattern B exhibited a significantly greater increase in LDL peak particle diameter and large LDL IIa and IIb and significantly greater decreases in small LDL IIIa, IIIb, and IVa compared with patients with pattern A. These differences in response between patients with LDL pattern A and those with pattern B were not reflected by changes in the standard lipid profile, including apoproteins A-I and B. Nicotinic acid has a significantly different effect on lipids and lipoprotein subclass distribution in subjects classified as having LDL subclass pattern A or B. Nicotinic acid has a significantly greater effect on the decrease of small LDL subclass distribution and increase in LDL peak particle diameter in pattern B versus pattern A.

Small dense LDL phenotype is associated with postprandial increases of large VLDL and remnant-like particles in patients with acute myocardial infarction

Background: The small dense low-density lipoprotein (LDL) phenotype (pattern B), high concentrations of remnant-like particles (RLPs), and postprandial lipemia are newly recognized risk factors for coronary heart disease (CHD). However, the associations of these lipoprotein abnormalities remain unclear. The aim of this study was to investigate the relationships among LDL phenotype, very-low-density lipoprotein (VLDL) subclasses, and postprandial lipoprotein metabolism in CHD patients. Method: We performed an oral fat tolerance test in 32 patients with acute myocardial infarction and compared the following parameters between patients characterized by either large buoyant LDL (pattern A) versus pattern B: lipids and apolipoproteins (apo) in the plasma and Svedberg flotation rates (Sf) >400 (chylomicron), Sf 60–400 (large VLDL), and Sf 20–60 (small VLDL) fractions. Result: Fasting levels of triglyceride, RLP-cholesterol and RLP-triglyceride were slightly higher in the pattern B patients. Postprandial increases of RLP-cholesterol and the cholesterol and triglyceride of large VLDL fractions were significantly greater in the pattern B patients. The areas under the curves of cholesterol, triglyceride, and apo-B in large VLDL fractions were significantly higher in pattern B, while those in small VLDL were not. RLP-cholesterol and RLP-triglyceride in fasting and fed states correlated very highly with the corresponding cholesterol and triglyceride concentrations in large VLDL fractions. Conclusion: These results suggest that postprandial increase of large VLDL fractions and RLPs contribute to the formation of small dense LDL in CHD patients.

Low-density-lipoprotein peak particle size in a Mediterranean population.

The predominance of small, dense low-density lipoprotein (LDL) particles ('LDL phenotype B') has been associated with a three-fold increased risk of myocardial infarction, but the feasibility of the identification of small, dense LDL as independent predictors of coronary artery disease risk in population studies remains questioned. Design We evaluated the LDL peak particle size and its relation with other established risk factors for coronary heart disease in a group of 156 randomized subjects living on the Mediterranean island of Ustica (71 males and 85 women, range of age 20-69 years), representing approximately 30% of the total population. The prevalence of LDL phenotype B subjects was low (approximately 15% in both men and women) and there was a clear trend for both genders in reducing the LDL peak particle size with age. Moreover, LDL phenotype B subjects had higher BMI values, prevalence of diabetes and plasma triglyceride (TG) levels and lower plasma HDL-C concentrations in comparison with LDL phenotype A individuals; in a multivariate analysis, plasma TG levels were the only variable independently associated with LDL peak particle size. In this population, which appears to be somewhat protected by premature coronary artery disease, a low prevalence of the LDL pattern B was found in both men and women, and plasma TG could have a key role in regulating the LDL peak particle size. The follow up, still ongoing, will provide useful information on the predictive role of LDL peak particle size on cardiovascular risk, at least in a low-risk population.

A short-run new analytical ultracentrifugal micromethod for determining low-density lipoprotein sub-fractions using Schlieren refractometry

We have developed a new analytical ultracentrifugal micromethod for the determination of serum low-density lipoprotein (LDL) subclasses directly from ultracentrifugal Schlieren scans. We have used special software for the analysis of this type of single-spin density-gradient ultracentrifugation. The flotation of LDL patterns was obtained by underlayering a physiological salt solution with serum or isolated lipoprotein fractions raised to a density of 1.3 g/mL in the spinning ultracentrifugation capillary band-forming cell. The repeated analysis of Schlieren curves of the same sample from 10 to 100 microL in the 60-100 min full-speed interval time resulted in quite reproducible results. We obtained quantitative results by measuring the Schlieren areas between the sample curves and the reference baseline curve by using computerised numerical and graphic techniques. The decomposition of the integrated curve was carried out using a nonlinear regression program followed by deconvolution algorithm analysis in order to determine the parameters of the composing Gaussian subclasses. The LDL particle concentrations were calculated from the area under the integral of the Gaussian curve using a calibration data constant. The flotation range of the LDL Schlieren curves in the cell was identified with serum from which LDL had been removed by means of precipitation reagents and with centrifugation of isolated LDL aliquots. With this technique, we measured the concentration of LDL and analysed its polydispersity without the need for preceding sequential isolation of the LDL. On the basis of the Schlieren curves, the LDL samples were either physically paucidisperse, having a symmetrical peak within a narrow density range, or were polydisperse, showing an asymmetrical pattern distributed over a broader density region. The described method proved to be useful for a clear and immediate visual presentation of the concentration values of the LDL and for the identification of the heterogeneity of LDL variants without the need for the preparative isolation of that density class.

Heart Stopper Genes: Would You Recognize a High Risk Patient?

Coronary artery disease (CAD) is one of the leading causes of death in the United States. Eighty percent of people having heart attacks have normal cholesterol levels. A quarter of the population have a condition called low-density lipoprotein (LDL) pattern B that has been associated with a threefold risk of myocardial infarction. Although early intervention can often prevent an otherwise fatal event, these patients often go unrecognized until after a myocardial infarction has occurred because they may not have the usual risk factors associated with cardiovascular disease. In patients with LDL pattern B, the standard lipid panel may be normal and inadequate for diagnosis and treatment of the condition. This article discusses how to identify a potentially high risk patient, available laboratory tests, management options, and the role of nurses in identifying high risk patients. The second author tells his personal story of surviving multiple cardiac arrests at a young age before being diagnosed with this condition.

Garlic powder, effect on plasma lipids, postprandial lipemia, low-density lipoprotein particle size, high-density lipoprotein subclass distribution and lipoprotein(a)

OBJECTIVESTo test the hypothesis that a garlic supplement alters plasma lipoproteins, postprandial lipemia, low-density lipoprotein (LDL) size and high-density lipoprotein (HDL) subclass distribution differently in 50 moderately hypercholesterolemic subjects classified as LDL subclass pattern A or B.BACKGROUNDGarlic has been variably reported to reduce or not affect plasma cholesterol values. Low-density lipoprotein pattern B is a common inherited disorder of lipoprotein metabolism that has been shown to have a significantly greater response to several lipid lowering treatments including low fat diet when compared with LDL pattern A individuals.METHODSA double blind, randomized, placebo controlled trial in an outpatient lipid research clinic was performed and included fifty moderately hypercholesterolemic subjects (mean LDL cholesterol = 166 ± 22 mg/dl) classified as LDL subclass pattern A (predominantly large LDL, n = 22) or B (predominantly small LDL, n = 28). Following a two-month stabilization period, subjects were randomly assigned to a placebo or 300 mg three times a day of a standardized garlic tablet for three months.RESULTSFor all subjects, LDL pattern A and B subjects combined, garlic treatment for three months resulted in no significant change in total cholesterol, LDL cholesterol, HDL cholesterol, HDL subclass distribution, postprandial triglycerides, apolipoprotein B, lipoprotein (a) (Lp[a]), LDL peak particle diameter or LDL subclass distribution. There was no significant difference in response for the same parameters among subjects classified as LDL pattern A or B with the exception of significantly greater (p = 0.01) reduction in mean peak particle diameter in pattern A subjects treated with either garlic or placebo. There was no significant change in LDL subclass distribution.CONCLUSIONSThis investigation confirms that garlic therapy has no effect on major plasma lipoproteins and further, that it has no impact on HDL subclasses, Lp(a), apolipoprotein B, postprandial triglycerides or LDL subclass distribution. Garlic may have a greater effect on LDL particle diameter in LDL pattern A compared with pattern B subjects. This difference was not reflected in other plasma lipid measurements.

Hypertriglyceridemia characterized by low-density lipoprotein phenotype and lipoprotein lipase gene mutation.

A high serum triglyceride (TG) concentration is associated with an increased serum concentration of small, dense low-density lipoprotein (LDL). To further characterize the hypertriglyceridemic condition, we examined sera from 240 subjects for small, dense LDL using non-denaturing polyacrylamide gradient gel electrophoresis. We focused on determining the frequency of the pattern B, which is characterized by a higher proportion of small, dense LDL, among hypertriglyceridemic individuals. The subjects were divided into four groups: a control group (TG < or = 1.65 mmol/l, high-density lipoprotein cholesterol (HDL-C) > or =1.17 mmol/l; n = 71), a high TG group (TG > 1.65 mmol/l, HDL-C > or = 1.17 mmol/l; n = 36), a group with high TG and low HDL-C (TG > 1.65 mmol/l, HDL-C < or = 0.91 mmol/l; n = 106), and a low HDL-C group (TG < or = 1.65 mmol/l, HDL-C < or = 0.91 mmol/l; n = 27). We found that pattern B occurs at a high frequency mainly in individuals with high TG and low HDL-C levels. We also observed an increased percentage of LDL within the 20.0 nm to 25.5 nm particle diameter range in this group. Analysis of the lipoprotein lipase gene in this group showed that some mutations seem to be associated with small, dense LDL, resulting in LDL pattern B.