Journal of Clinical Lipidology

Editorial Board

2012-03-01

From the Editor

W. Virgil Brown — 2012-01-30

Medications that lower low-density lipoprotein (LDL) cholesterol and non–high-density lipoprotein (non-HDL) cholesterol have provided convincing proof that the latter are causative particles in the arteriosclerotic process. The mechanism of action of the most effective medications depends on lowering the cholesterol content of the liver and stimulating the expression of LDL receptors. However, there are certain conditions in which these medications are not effective, most notably, in patients with little ability to synthesize or deliver fully functional LDL receptors to the cell membranes. Such patients are not sufficiently responsive to statins, bile acid binding resins, ezetimibe, or any other current medications. The research into mechanisms that reduce apolipoprotein B synthesis show promise for improved therapy in this circumstance. These include the antisense oligonucleotides, like mipomersen, but none of these are yet fully documented by adequate clinical trials. It is estimated that 0.2% of most populations have either homozygous familial hypercholesterolemia (same genetic defect in both chromosomes) or compound heterozygous familial hypercholesterolemia (different defects existing in the two alleles). Rarely, other genetic defects may cause dysfunction of the LDL receptor and lead to high LDL values. Unfortunately, these disorders produce arteriosclerosis in very young children and without effective treatment, all the consequences of this process are seen in youth and early middle age.

News from the NLA

2012-02-13

Submit your research for presentation as a poster during the NLA Annual Scientific Sessions in Scottsdale, AZ. The deadline for poster abstract submissions is April 2, 2012. All accepted poster abstracts will be published in the May/June 2012 issue of the Journal of Clinical Lipidology. In addition to posters being displayed at the meeting during the designated hours, selected abstract submissions will be identified for an oral presentation session on Saturday, June 2.

The use of lipopheresis in the practice of clinical lipidology†

W. Virgil Brown, Robert Brook, Linda C. Hemphill, Patrick M. Moriarty — 2011-12-23

W. Virgil Brown, MD: In this issue of the Journal, I have invited three clinical lipidologists who are treating patients with very high LDL concentrations using devices that physically remove apolipoprotein B (apoB)-containing lipoproteins from the blood. We have discussed the clinical use of these methods that trap lipoproteins in physical systems while directly connected to the vasculature. Although extremely efficacious in the short term, they require repeated use to achieve the longer-term effects necessary to successfully reduce vascular disease risk. The several methods in this arena have become known as lipopheresis or lipoprotein apheresis. Dr. Robert Brook, from the University of Michigan, Dr. Linda Hemphill, from Harvard, and Dr. Patrick Moriarty, from the University of Kansas, have agreed to answer my questions regarding the appropriate applications of these procedures.

Polish Lipid Association – A strong response to the problem of lipid disorders in Poland and Central and Eastern Europe

Maciej Banach, Michael Davidson, Peter P. Toth — 2011-12-12

As a group, lipid disorders constitute one of the most important and common risk factors for atherosclerotic disease. According to the cardiovascular continuum theory, lipid disorders promote the development of atherosclerosis and its clinical sequelae, including acute coronary syndromes (ACS), ischemic stroke, peripheral arterial disease, heart failure, and sudden cardiac death. Despite the introduction of very effective lipid-modifying drugs, hyperlipidemia is still poorly controlled and treated worldwide.

Genotype–phenotype correlation related to lipid profile in beta-thalassemia major and intermedia in southern Iran

2011-12-28

Background: Beta-thalassemia is commonly associated with lipid abnormalities. The aim of this study was to search for links between these lipid alterations and different types of β-thalassemia mutations.Methods: The study, conducted from 2009 to 2010, included 100 patients with thalassemia major (TM) and 100 with thalassemia intermedia (TI). The control group was selected from 100 age- and sex-matched healthy individuals with normal hematologic indices. Serum lipid profiles, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG), were determined and their relationship with different covariates, including different β-globin gene mutations, was analyzed.Results: Patients with TI had significantly lower values for TC, LDL-C, HDL-C, and LDL-C/HDL-C ratio compared with TM patients and controls (P < .001). TG was greater in TM compared with TI patients (P = .001) and healthy individuals (P = .007). Hemoglobin was positively associated with TC (P < .001), LDL-C (P = .004), and HDL-C (P = .01) in TM patients. Splenectomy correlated with greater TC (P = .006) and LDL-C (P = .01) in TI patients, but only with greater LDL-C in TM patients (P = .02). The average amounts of TC and LDL-C were lower in persons with the β0/β0 mutation compared with the β+/β+ group.Conclusion: Lower amounts of TG, TC, LDL-C, and HDL-C were seen in TI patients compared with TM patients and healthy individuals. The severity of the genotype (ie, β0 type mutations compared with β+ type mutations) affected the degree of reduction in serum lipids.

Difference between calculated and direct-measured low-density lipoprotein cholesterol in subjects with diabetes mellitus or taking lipid-lowering medications

2011-12-26

Objective: We evaluated factors that caused differences between calculated low-density lipoprotein cholesterol (C-LDL-C) and direct-measured LDL-C (D-LDL-C) and compared them in subjects with diabetes mellitus (DM) or taking lipid-lowering medications.Methods: 21,452 subjects (9,177 women, 12,275 men; 8.1% with DM and 8.5% on lipid-lowering medications) were included in the analysis. Participants were classified into 3 groups, i.e., group 1: the subjects without DM and not on lipid-modifying drugs (n = 18,287), group 2: without DM and on lipid-modifying drugs (n = 1,423), and group 3: with DM (n = 1,742). LDL-C concentrations were either directly measured by a homogenous method or calculated by Friedewald formula.Results: There was a significant correlation between C-LDL-C and D-LDL-C (r = 0.966, P < .001). The absolute values of the differences between two LDL-C values were 7.0 ± 6.2 mg/dl and 6.6 ± 7.3% (6.6 ± 5.9 mg/dl and 6.0 ± 6.5%, 8.8 ± 6.7 mg/dl and 9.1 ± 9.7%, and 10.1 ± 7.3 mg/dl and 10.7 ± 10.1% in group 1, 2, and 3 respectively, P < .001). The subjects with the absolute value of the differences of LDL-C ≥10% was 20.2% (17.3%, 31.3%, and 41.1% in group 1, 2, and 3 respectively, P < .001). In the multiple logistic regression analysis, high triglyceride (≥150 mg/dl), low high-density lipoprotein cholesterol (HDL-C) (<40 mg/dl), male gender, obesity (body mass index ≥25 kg/m2), DM and taking lipid-lowering drugs were significant associated with high LDL-differences (the absolute value of the differences ≥10% or ≥10 mg/dl).Conclusion: D-LDL-C was generally higher by 5 mg/dl or 5% than C-LDL-C. The differences C-LDL-C and D-LDL-C were higher in subjects with DM and on lipid-lowering medications. Male gender, high triglyceride, low HDL-C, and obesity were also associated with the greater differences between C-LDL-C and D-LDL-C.

A systematic review on evidence of the effectiveness and safety of a wax-matrix niacin formulation

Andrew P. Dunatchik, Matthew K. Ito, Carlos A. Dujovne — 2011-07-26

Abstract: Niacin is a uniquely efficacious therapy in the treatment of dyslipidemia because of its broad spectrum of beneficial effects on every aspect of the lipid profile and because it has been shown to reduce both total mortality and coronary death. However, niacin therapy is hindered by its side-effect profile, which appears to be dependent on its formulation with immediate-release niacin, associated with a greater incidence of flushing, and sustained-release niacin, associated with greater liver function test (LFT) abnormalities and hepatotoxicity. One such sustained-release niacin nutritional supplement formulation, Endur-acin (Endurance Products Company, Tigard, OR), claims to have clinical evidence to support its use in the treatment of dyslipidemias, which prompted us to systematically review the literature. We identified four published papers in which the authors reported the results of two separate clinical trials and one pharmacokinetic study that fulfilled the inclusion criteria and were included in this review. Endur-acin significantly reduced total cholesterol, low-density lipoprotein cholesterol, and total cholesterol/high-density lipoprotein cholesterol ratio with mean reductions up to 19%, 26%, and 20%, respectively, at a dose of 2000 mg/day. Less-impressive benefits were also seen with high-density lipoprotein cholesterol (+10%) and serum triglycerides (−23%). Mean LFT elevations of up to 1.6-fold were seen at the 2000 mg per day dose, however, not exceeding three times the upper limit of normal, with abnormal results occurring at similar frequency in placebo and one patient experiencing marked gastrointestinal symptoms and a hepatitis-like syndrome with reversible elevated LFT. Short-term randomized controlled trials suggest Endur-acin is effective in modifying serum lipids, although study limitations prevent a comprehensive evaluation of safety.

Lipid levels in obese and nonobese subjects as predictors of fasting and postload glucose metabolism

2011-10-03

Background: Dyslipidemia in the overweight/obese patient often is associated with impaired glucose metabolism. The authors of large clinical trials in different ethnic groups highlighted the correlation between glycemia and lipid profile, although the effect of abdominal adiposity was not explored.Objective: To evaluate the relationship of visceral adiposity and lipid profile with fasting (FPG) and postload glucose (2hPG) in subjects without known diabetes (DM2).Methods: A total of 3030 subjects were divided in three groups: obese subjects (OB; n = 490), nonobese subjects with an increased waist circumference (NOB/W+; n = 500), and nonobese subjects without an increased waist circumference (NOB/W−; n = 2040). We performed a linear regression analysis among lipid fractions and fasting and 2hPG in the three groups, with or without diagnosis of DM2 after 2hPG.Results: Our data confirmed the significant association (P < .01) of high triglycerides and low high-density lipoprotein cholesterol (HDL-C) with fasting and 2hPG in all three groups such as for non-HDL cholesterol, whereas total cholesterol (TC) showed a significant correlation only with fasting glucose in OB and NOB/W+ subjects (P < .01). The analysis with or without DM2 demonstrated no difference in the statistical significance, although a better correlation in subjects without DM2 was observed. In addition, for each quartile of TC a significant trend (P < .01) in prevalence of fasting hyperglycemia in obese and in NOB/W+ patients was observed.Conclusion: This study suggests that triglycerides and HDL-C, together with non-HDL cholesterol, are associated with impaired fasting and 2hPG and that high total cholesterol levels are associated with abnormalities of fasting glucose metabolism only in patients with elevated waist circumference.

Pregnancy during adolescence has lasting adverse effects on blood lipids: A 10-year longitudinal study of black and white females

2011-12-26

Background: Primiparity has been associated with 3 to 4 mg/dL lower high-density lipoprotein cholesterol concentrations in black and white adult women that persist several years after delivery.Objective: To examine the lasting effects of adolescent pregnancy on blood lipids, an early risk factor for future cardiometabolic diseases.Design: The National Heart Lung and Blood Institute’s Growth and Health Study is a multicenter prospective cohort that measured fasting blood lipids for 1013 (513 black, 500 white) participants at baseline (1987–1988) ages 9–10, and again at follow-up (1996–1997) ages 18–19.Methods: Change in fasting plasma total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, defined as the difference between baseline and follow-up measurements, was compared among 186 (145 black, 41 white) primi- or multiparas, 106 (55 black, 51 white) nulliparous, gravidas versus 721 (313 black, 408 white) nulligravidas. Fully adjusted multiple linear regression models estimated blood lipid changes among these pregnancy groups adjusted for race, age at menarche, baseline lipids, physical inactivity, body mass index, and family sociodemographics.Results: In the 10-year study period, adolescent paras compared with nulligravidas had greater decrements in high-density lipoprotein cholesterol (mg/dL; fully adjusted mean [95% confidence interval] group differences in black −4.3 [−6.7, −2.0]; P < .001 and white: −4.5 [−8.2, −0.7]; P = .016) and greater increments in fasting triglycerides (mg/dL; adjusted mean [95% confidence interval] group differences in black: 10.4 [3.9, 16.8]; P < .001, and white: 11.6 [−3.6, 26.8]; P = .167).Conclusion: Adolescent pregnancy contributes to pro-atherogenic lipid profiles that persist after delivery. Further research is needed to assess whether adolescent pregnancy has implications for future cardiovascular disease risk in young women.

A multicenter study of nutraceutical drinks for cholesterol (evaluating effectiveness and tolerability)

Mitchell Karl, Mark Rubenstein, Chad Rudnick, John Brejda — 2011-09-22

Background: We hypothesized that a nutraceutical formulation containing small amounts of bioactive constituents that exert cholesterol-lowering effects by different mechanisms may exhibit synergistic efficacy with a clean tolerability profile. The purpose of this study was to evaluate nutraceutical fruit-flavored drinks with and without red yeast rice (RYR) for effects on low-density lipoprotein (LDL) and total cholesterol.Methods: In double-blinded fashion, 79 subjects were randomized to one of three fruit-flavored drinks, ie, a placebo, and two active drinks containing niacin, phytosterol esters, L-carnitine, vitamin C, and Co-Q-10, one with and without RYR, twice daily. Primary end points were LDL and total cholesterol percent reductions from baseline. Secondary end points were high-density lipoprotein and C-reactive protein percent change from baseline. Physician contact and laboratory work were obtained at baseline, 4 weeks, and 8 weeks of subject participation.Results: A total of 59 subjects completed the study. The placebo group and the group receiving the nutraceuticals without RYR showed no change in primary or secondary end points. The nutraceutical drink with RYR reduced total cholesterol at week 4 by 13% (−35 mg/dL) and week 8 by 14% (−46 mg/dL). LDL cholesterol decreased 17.1% at 4 weeks (−28 mg/dL) and 17.8% at week 8 (−30 mg/dL). In the effective drink arm containing nutraceuticals and RYR there were no biochemical or subjective intolerance, with the exception of one subject who experienced headache.Conclusions: A nutraceutical drink with RYR can be a safe and effective natural alternative to pharmacologic therapies for people intolerant to or refusing statins but still in need of achieving and maintaining a healthy and low cholesterol level.

Relationship between serum uric acid and metabolic syndrome: An analysis by structural equation modeling

2011-12-06

Objective: To investigate the nature of the relationships between uric acid and metabolic syndrome (MetS) components.Methods: Body mass index, waist circumference, serum uric acid, fasting glucose, lipid profiles, and blood pressure were measured in 13,811 subjects aged between 18 and 85 years of age. Two structural equation models (SEMs) were used to test a hypothesis regarding the linking roles of uric acid in the occurrence of MetS components in male and female separately.Results: The findings of the SEM demonstrated that increased uric acid level was associated with fasting glucose (beta = 0.221, P < .001), blood pressure (beta = 0.158, P < .001), and lipid profiles (beta = 0.391, P < .001) in women. Increased uric acid level was associated with decreased fasting glucose (beta = −0.071, P < .001) and increased lipid profiles (beta = 0.352, P < .001) in men. The association was stronger between uric acid and lipid profiles than those between uric acid and other MetS components.Conclusion: By using SEM, we were able to confirm the intimate relationships between uric acid and MetS components, particularly in women. The associations between uric acid and MetS components were gender specific, and the nature of such association requires further exploration.

Elevation of fasting morning glucose relative to hemoglobin A1c in normoglycemic patients treated with niacin and with statins

2011-12-26

Background: Niacin increases fasting glucose levels, and statins modestly increase the rate of new-onset diabetes. The clinical importance and mechanisms of these effects are not fully explored.Objective: On the basis of anecdotal observations, we hypothesized that elevated morning fasting glucose may be accompanied by relatively normal hemoglobin A1c (HbA1c) in patients treated with niacin and other lipid-modifying drugs. We conducted a retrospective cohort analysis to test this hypothesis.Methods: The Duke Lipid Clinic database (1994–2007) was screened for simultaneous determinations of fasting morning glucose and HbA1c, yielding 1483 data pairs among 554 subjects. Subjects with diabetes, by clinical diagnosis, medication, or any HbA1c ≥6.5%, or nondiabetes were analyzed separately. Repeated-measures linear regression featured glucose as dependent variable and included terms for HbA1c, drug(s), and their interaction.Results: Regression lines for glucose on HbA1c had altered slopes in the presence of niacin and/or statin use in normoglycemic subjects. The corresponding interaction terms (drug and HbA1c) were significant (niacin P = .026, statin P = .013). Fibrate use had no effect (interaction P = .49). When modeled together, niacin and statin effects were independent. Regression curves in diabetic patients were not affected by lipid medications.Conclusion: Elevated fasting glucose may be accompanied by relatively normal HbA1c in niacin- and statin-treated patients. HbA1c reflects average daily glucose levels and is likely a better measure of the glycemic effect of lipid medications. Because our data were retrospective, confirmation from randomized trials is needed.

The relationship between subclinical atherosclerosis, non–high-density lipoprotein cholesterol, exercise, and diet among male participants of the PACC Project

Lauren A. Simprini, Todd C. Villines, Michael Rich, Allen J. Taylor — 2011-12-05

Background: Non-high-density lipoprotein (HDL) cholesterol is recommended as a secondary lipid goal treated initially with lifestyle modification. However, the relationship between non-HDL and subclinical atherosclerosis is unknown. We examined the independent relationships between coronary artery calcium (CAC), lipids including non-HDL, exercise, and diet among healthy male participants of the Prospective Army Coronary Calcium (PACC) Project.Methods: Male participants from the PACC Project (n = 1637, mean age 42.8 years; no history of coronary heart disease) were studied. We used validated surveys to measure dietary quality and habitual physical exercise. Fasting lipid concentrations and other cardiovascular risk variables were measured. Subclinical atherosclerosis was detected with the use of electron beam computed tomography for CAC. Factors independently associated with the presence of any detectable CAC (CAC score > 0), including standard CV risk variables, non-HDL, exercise, and diet, were evaluated with the use of logistic regression.Results: The mean Framingham risk score was 4.6 ± 2.6%; CAC was present in 22.4%. Fasting lipid concentrations showed mean LDL-C 128 ± 32 mg/dL, HDL-C 50 ± 13 mg/dL, TG-C 130 ± 86 mg/dL, and non-HDL-C 154 ± 37 mg/dL. Men with CAC had significantly greater levels of LDL-C (135 vs 127 mg/dL), TG (148 vs 124 mg/dL), and non-HDL-C (164 vs 151 mg/dL) and less habitual physical activity (P = 0.006). There were nonsignificant trends between prevalent CAC, greater amounts of dietary fat intake, and lower HDL-C. In successive multivariable logistic regression models for the dependent variable CAC, only non-HDL-C (odds ratio [OR] 1.012 per mg/dL; 95% CI 1.002–1.023; P = .019) and age (OR 1.119 per year; 95% CI 1.063–1.178; P < .001) were independently associated with the presence of CAC, and exercise (OR 0.808; 95% CI 0.703–0.928; P = 0.003) was associated with the absence of CAC.Conclusions: Non-HDL-C and exercise are independently predictive of the presence of subclinical CAC among healthy lower-risk middle-aged men.

Changes in prescription patterns before and after reporting of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression trial (ENHANCE) results and expected effects on low-density lipoprotein-cholesterol reduction

2011-12-08

Background: Recent trends suggest a decreased use of ezetimibe/simvastatin combination and coadministered ezetimibe plus statin therapies.Objective: This analysis evaluated changes in prescription patterns for ezetimibe/simvastatin, ezetimibe plus statins, and statin therapies and expected effects on low-density lipoprotein cholesterol (LDL-C) lowering during 2007 to 2008.Methods: Prescription pattern changes were assessed by the use of patient-level data from the IMS Health Longitudinal Rx database during two time periods, July 14, 2007 to January 13, 2008 (n = 8,813,674) and January 14, 2008 to July 13, 2008 (n = 9,131,030), 6 months before and after reporting of the results of The Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression trial (ENHANCE) trial on January 14, 2008. Expected LDL-C reductions were estimated using data from previous controlled clinical trials.Results: During 6 months post-ENHANCE, greater proportions of patients were switched from ezetimibe/simvastatin and ezetimibe plus statins to other lipid-lowering therapies by health care providers than 6 months pre-ENHANCE (21.1% vs 6.0% and 46.9% vs 38.5%, differences: −15.06% [95% confidence interval −15.14%, −14.97%] and −8.43% [95% confidence interval −8.70%, −8.17%], respectively). Greater proportions of these patients switched to statin monotherapy in the later than earlier period. Prescription patterns were similar for statins during both time periods, although fewer patients switched to ezetimibe/simvastatin and ezetimibe plus statin therapies post-ENHANCE. In both time periods, greater proportions of patients on ezetimibe/simvastatin and ezetimibe plus statins switched to less-than-equivalent LDL-C lowering efficacy doses of statins than those on statin therapy. On the basis of previous clinical data for these therapies, smaller LDL-C reductions would be expected in patients who switched from ezetimibe/simvastatin and ezetimibe plus statins to statins, despite a trend toward switching to greater statin doses in the later time period.Conclusions: More patients switched from ezetimibe/simvastatin and ezetimibe plus statin to statin monotherapy 6 months after the reporting of the ENHANCE trial, the majority of which were prescribed less potent, LDL-C–lowering therapies. On the basis of the known LDL-C lowering efficacies for these therapies, such changes would be expected to increase LDL-C levels in these patients and may reduce the proportion of patients who achieve guideline-recommended LDL-C goals.

Low-density lipoprotein apheresis is effective in reducing lipoprotein(a) levels and in improving symptoms in a patient with refractory angina secondary to accelerated coronary artery disease

Michael Ibrahim, Bassey Ussen, Alison Pottle, Mahmoud Barbir — 2011-12-05

Abstract: Coronary artery disease remains a significant cause of morbidity and mortality in the Western world. High plasma Lp(a) concentrations are related to the risk of cardiovascular disease, but Lp(a) is rarely assayed and treated. We present the case of a 50-year-old gentleman with refractory angina, whose coronary disease continued to progress despite optimal medical and surgical therapy. We show that the aggressive reduction of Lp(a) successfully ameliorated the progression of coronary stenosis and provides effective and durable relief of symptoms.

Journal of Clinical Lipidology

Editorial Board

Table of Contents

From the Editor

News from the NLA

The use of lipopheresis in the practice of clinical lipidology†

Polish Lipid Association – A strong response to the problem of lipid disorders in Poland and Central and Eastern Europe

Genotype–phenotype correlation related to lipid profile in beta-thalassemia major and intermedia in southern Iran

Difference between calculated and direct-measured low-density lipoprotein cholesterol in subjects with diabetes mellitus or taking lipid-lowering medications

A systematic review on evidence of the effectiveness and safety of a wax-matrix niacin formulation

Lipid levels in obese and nonobese subjects as predictors of fasting and postload glucose metabolism

Pregnancy during adolescence has lasting adverse effects on blood lipids: A 10-year longitudinal study of black and white females

A multicenter study of nutraceutical drinks for cholesterol (evaluating effectiveness and tolerability)

Relationship between serum uric acid and metabolic syndrome: An analysis by structural equation modeling

Elevation of fasting morning glucose relative to hemoglobin A1c in normoglycemic patients treated with niacin and with statins

The relationship between subclinical atherosclerosis, non–high-density lipoprotein cholesterol, exercise, and diet among male participants of the PACC Project

Changes in prescription patterns before and after reporting of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression trial (ENHANCE) results and expected effects on low-density lipoprotein-cholesterol reduction

Low-density lipoprotein apheresis is effective in reducing lipoprotein(a) levels and in improving symptoms in a patient with refractory angina secondary to accelerated coronary artery disease