Comparing a novel equation for calculating low-density lipoprotein cholesterol with the Friedewald equation: A VOYAGER analysis

Treating elevated low-density lipoprotein cholesterol (LDL-C) to risk-stratified target levels is recommended in several guidelines. Thus, accurate estimation of LDL-C is required. LDL-C is typically calculated using the Friedewald equation: (total cholesterol) – (non-high-density lipoprotein cholesterol [non-HDL-C]) – (triglycerides [TGs]/5). As the equation uses a fixed value equal to 5 as a divisor for TGs, it does not account for inter-individual variability, often resulting in underestimation of risk and potentially undertreatment. It is specifically inapplicable in patients with fasting triglycerides ≥400 mg/dL. A novel method of LDL-C calculation was derived and validated by Martin et al.: (non-HDL-C) – (triglycerides/adjustable factor). This equation uses an adjustable factor, the median TG:very-low-density lipoprotein cholesterol ratio in strata defined by levels of TG and non-HDLC, as divisor for TGs, and the adjustable factor ranging from 3 to 12 has been shown to provide more accurate estimates of LDL-C compared with the Friedewald equation using a direct assay as the gold standard.We used 70,209 baseline and on-treatment lipid values from the VOYAGER meta-analysis database to determine the difference in calculated LDL-C values using the Friedewald and novel equations. In patients with TGs <400 mg/dL, LDL-C values calculated using the novel equation were plotted against those calculated using the Friedewald equation. The novel equation generally resulted in LDL-C values greater than the Friedewald calculation, with differences increasing with decreasing LDL-C levels; 23% of individuals who reached a LDL-C target of 70 mg/dL with the Friedewald equation did not achieve this target when the novel equation was used to calculate LDL-C; these figures were 8% and 2% for <100 mg/dL and < 130 mg/dL targets, respectively. In patients with triglycerides ≥400 mg/dL, in whom the Friedewald equation is not valid, lipid values calculated using the novel equation were compared with those obtained by β-quantification. Values calculated with the novel equation did not appear to be closely related with those calculated by β-quantification in these patients. In conclusion, the novel equation provides a higher estimation of exact LDL-C values than the Friedewald equation, particularly in patients with low LDL-C levels, which may result in undertreatment of some patients whose LDL-C was calculated using the Friedewald method. However, neither may be suitable for patients with TG ≥400 mg/dL.     

An open-label comparison of the effects of simvastatin and niacin alone and combined on the lipid profile and lipoprotein (a) level in an Indian population with dyslipidemia

Abstract

Background:

Patients with dyslipidemia often require the use of >1 lipid-altering agent to achieve the target levels recommended by the National Cholesterol Education Program Adult Treatment Panel III.

Objective:

The aim of this study was to compare the effects of simvastatin and niacin alone and combined on the lipid profile and lipoprotein (a) (Lp[a]) level in an Indian population with dyslipidemia.

Methods:

This 12-week, open-label, nonrandomized study was conducted at the Departments of Pharmacology and Medicine, Government Medical College, Amritsar (Punjab), India. Patients aged 30 to 70 years with dyslipidemia were eligible. Patients were assigned to 1 of 3 treatment groups. Group 1 received simvastatin 20 mg/d for 12 weeks. Group 2 received niacin at doses of 375 mg/d for 1 week, 500 mg/d for 1 week, and 500 mg BID for 10 weeks. Group 3 received simvastatin 10 mg/d plus niacin (375 mg for 1 week and 500 mg for 11 weeks). The lipid profile (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and triglycerides [TG]) and Lp(a) were measured before the start of therapy and at 6 and 12 weeks of treatment. Percentage changes from baseline were calculated. Adverse effects (AEs) were recorded at weeks 6 and 12 and through spontaneous reporting.

Results:

Ninety patients were enrolled (50 men, 40 women; 30 patients per treatment group). In group 1, the mean (SD) percentage decrease in LDL-C level at 12 weeks was 42.79% (16.29%) (P < 0.05), but no significant change was seen in group 2 or 3. The mean (SD) percentage increases in HDL-C level were 18.43% (13.28%) and 20.82% (17.57%) in groups 2 and 3, respectively (both, P < 0.05), but no significant change was seen in group 1. TC levels decreased by a mean (SD) of 32.97% (13.66%) in group 1 (P < 0.05), but no significant change was seen in group 2 or 3. TG and Lp(a) levels did not change significantly in any of the 3 treatment groups. Flushing, myalgia, and dyspepsia were the most common AEs in patients receiving niacin.

Conclusions:

In this study in Indian patients with dyslipidemia, simvastatin-niacin combination therapy was associated with greater changes in lipid profile compared with either agent used alone. Niacin was also associated with greater changes in Lp(a) levels. AEs were less prevalent with combination therapy than with niacin alone.Key words: dyslipidemia, simvastatin, niacin, combination therapy     

Lipoprotein apheresis in the management of severe hypercholesterolemia and hyperlipoproteinemia(a)—The Portuguese experience

Background

Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) are established causal risk factors for cardiovascular disease (CVD). Lipoprotein apheresis is often required for treatment of patients with a high risk for CVD due to hypercholesterolemia and/or hyperlipoproteinemia(a).

Evaluation of alternative calculation methods for determining low-density lipoprotein cholesterol in hemodialysis patients

OBJECTIVES: To evaluate alternative equations for the estimation of low-density lipoprotein cholesterol (LDL-C) than the Friedewald equation in hemodialysis patients. DESIGN AND METHODS: The equations LDL-C = 0.41TC - 0.14TG + 0.66ApoB - 10.43 and LDL-C = 0.94TC - 0.94HDL-C - 0.19TG were evaluated in 86 patients and compared with the Friedewald equation and the ultracentrifugation procedure. RESULTS: The alternative equations yield significantly lower bias than the Friedewald equation and are less affected by increased triglycerides (TG) levels. CONCLUSION: The alternative equations for LDL-C yield slightly better results than the Friedewald equation especially in hypertriglyceridemia.     

Efficacy and Safety of Morning Versus Evening Dose of Controlled-Release Simvastatin Tablets in Patients With Hyperlipidemia: A Randomized,Double-Blind,Multicenter Phase III Trial

Background

Flexibility in the recommended dosing time for a statin may improve patient compliance.

Objective

This study was designed to compare the efficacy and tolerability of morning and evening doses of controlled-release simvastatin in Korean adults with dyslipidemia. It was carried out as a requirement to obtain authorization from the Korean regulatory agency to market the product.

Methods

In this prospective, randomized, double-blind, multicenter, placebo-controlled Phase III study, we randomly assigned 132 patients with hypercholesterolemia to a morning-dose group or an evening-dose group. Patients in the morning-dose group received 20 mg controlled-release simvastatin in the morning and a placebo in the evening, and those in the evening-dose group received a placebo in the morning and 20 mg controlled-release simvastatin in the evening.

Results

After 8 weeks of the treatment, the difference in the mean change of LDL-C between the morning-dose and evening-dose groups was −2.78% (95% confidence interval, −7.65 to 2.10). The changes in total cholesterol, triglycerides, HDL-C, apolipoprotein A1, apolipoprotein B, and lipoprotein (a) after treatment did not differ between groups. Also, the achievement rates of the target LDL-C goal suggested by the dyslipidemia treatment guideline of the Korean Society of Lipidology and Atherosclerosis were not different. No serious adverse event was observed in either group. Mild and moderate adverse events were observed similarly in both groups.

Conclusions

Although controlled-release simvastatin significantly reduces LDL-C levels with good tolerability in Korean adults with dyslipidemia, the time of administration does not affect its efficacy.     

Three different LDL apheresis columns efficiently and equally reduce lipoprotein(a) concentrations in patients with familial hypercholesterolemia and small apolipoprotein(a) particles

Introduction

High levels of lipoprotein(a) [Lp(a)] and apolipoprotein(a) [apo(a)] are associated with cardiovascular disease. In this study we determined apo(a) particle size and compared the Lp(a) reducing efficacy of three different LDL apheresis columns; DL-75, LA-15 and EC-50W in patients with familial hypercholesterolemia (FH).

Results

Average Lp(a) concentration was reduced by 70%, 74% and 75% (all p < 0.0001) for DL-75, LA-15 and EC-50W, respectively. No significant changes in the relative proportion of the isoforms of 14 and 32 K 4 domains were observed after apheresis.

Conclusion

Three different LDL apheresis columns reduced Lp(a) efficiently with preserved ratio between apo(a) isoforms.     

Heterogeneous properties of intermediate- and low-density lipoprotein subpopulations

Objective

Intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) consist of heterogeneous particles whose subpopulations may have different atherogenic characteristics. This study investigated the associations between these subpopulations and other lipids, lipoproteins and atherosclerosis-related markers.

Design and methods

A total of 416 subjects (124 males and 292 females, mean age: 50.8 years) were enrolled in this study. Using polyacrylamide gel electrophoresis, serum lipoproteins were separated according to their specific electrophoretic mobility based on particle size. The IDL particles were separated into three midbands (MID-A to C), and the LDL particles were separated into seven subfractions (LDL1 to 7).

Results

MID-B, MID-C, LDL2 and LDL3 to 6 (as a small LDL fraction) were significantly and positively correlated with very LDL (VLDL), while MID-A and LDL1 were significantly and inversely correlated with VLDL. MID-A and LDL1 were significantly and positively correlated with high-density lipoprotein (HDL). The correlation patterns between MID-A or LDL1 and triglycerides, apolipoprotein A-I, glucose, the insulin resistance index, creatinine and the mean LDL particle size had similar trends to those between HDL and these parameters.

Conclusions

The respective subpopulations of IDL and LDL particles can vary in their ability to predict cardiovascular disease risks. These variations may partially explain why quantitative assessments using LDL-cholesterol concentrations, as typically performed in conventional practice, are not perfect predictors of cardiovascular disease. Further studies are required to determine the clinical relevance of analyzing the IDL and LDL subpopulations.     

Assessment of apoB dyslipoproteinemia in Korean population

Objectives

There is sparse data on apoB dyslipoproteinemia in Asian population. The purpose of this study was to assess apoB dyslipoproteinemia and to compare the LDL-C, non-HDL and apoB for risk assessment with percentile equivalent cut off in Korean population.

Methods

With 1193 Korean adult subjects, the prevalence and characteristics of different types of dyslipoproteinemias were analyzed in each age and gender group. The percentile values of direct LDL-C, calculated LDL-C, non HDL-C, HDL-C, apoAI, apoB and apoB/apoAI ratio were estimated.

Results

The prevalences of normoapoB–hyperTG, hyperapoB–normoTG and hyperapoB–hyperTG dyslipoproteinemia were 6.9, 8.9 and 10.9% in men and 3.7, 6.4 and 2.8% in women. The 40th percentile of direct LDL-C, calculated LDL-C, non-HDL-C and apo B were 108, 104.2, 126 and 85 mg/dl, respectively. The individual above optimal cut off was significantly underestimated with LDL-C than with non-HDL and apoB, in groups with adverse risk factors.

Conclusions

This study firstly shows the prevalence of various types of dyslipoproteinemias in Asian population. The percentile values of Korean population were similar to those of NHANES. Integration of lipid markers is needed for making clinical decisions and further research involving various populations and methodologies should be performed.     

The Efficacy of Colesevelam HCl in the Treatment of Heterozygous Familial Hypercholesterolemia in Pediatric and Adult Patients

Background

Familial hypercholesterolemia (FH) is a common autosomal co-dominant genetic disorder that results in severely increased levels of LDL-C. Patients with FH are at an increased risk for premature coronary artery disease. Expert panels therefore recommend initiation of lipid-lowering therapy in childhood to reduce the very high lifetime risk of coronary artery disease. The bile acid sequestrant colesevelam is indicated to reduce elevated LDL-C levels in adults with primary hyperlipidemia and in boys and postmenarchal girls (aged 10–17 years) with heterozygous FH.

Objective

The purpose of this article was to review currently available data on the use of colesevelam in the treatment of heterozygous FH.

Methods

PubMed and Google Scholar were searched to identify clinical trials evaluating colesevelam in patients with heterozygous FH.

Results

The search returned 2 results (both multicenter, multinational studies): 1 study conducted in adults and the other in pediatric patients. In the study in adults with refractory FH, the addition of colesevelam to a maximally tolerated regimen of a statin plus ezetimibe provided a significantly greater reduction from baseline in LDL-C levels compared with placebo. Significantly greater reductions from baseline in LDL-C were also seen in pediatric patients with heterozygous FH receiving colesevelam (alone or in combination with statins) compared with placebo. Colesevelam was generally well tolerated in studies in patients with FH; consistent with other colesevelam studies, gastrointestinal disorders were the most common drug-related adverse events, but these events rarely led to study withdrawal.

Conclusions

Currently available data demonstrate that colesevelam, alone or in combination therapy, is efficacious and well tolerated in the treatment of heterozygous FH in adults and pediatric patients, supporting its use as a treatment option in both of these patient populations.     

LDL cholesterol estimation using the Anandaraja's and Friedewald's formulas in schizophrenic patients treated with antipsychotic drugs

Objectives

The use of new antipsychotic drugs is associated with an increased risk of diabetes and metabolic syndrome, and the routine monitoring of blood lipids during treatment has been recommended. Recently, a new formula for the estimation of low-density lipoprotein (LDL) cholesterol from total cholesterol and triglycerides has been proposed by Anandaraja et al. (Int J Cardiol 2005; 102: 117), and the aim of our study was its evaluation in schizophrenic patients treated with antipsychotic drugs.

Materials and methods

In 487 serum samples from schizophrenic patients treated with clozapine in polytherapy, the concentrations of LDL cholesterol were determined by agar gel electrophoresis and the formula of Friedewald et al. (Clin Chem 1972; 18: 499), and compared with the results of the Anandaraja's formula.

Results

A higher correlation and lower error of the estimate of the electrophoresis results was found with those of Friedewald (r = 0.940, ma68 = 0.17 mmol/L) than those of Anandaraja (r = 0.811, ma68 = 0.31 mmol/L). Similar results were obtained on making a dichotomy of the patients with and without metabolic syndrome lipid profile. A highly significant correlation was found between the high-density lipoprotein (HDL) cholesterol levels and the Anandaraja/Electrophoresis (r = 0.817, p < 0.001) and Anandaraja/Friedewald (r = 0.977, p < 0.001) ratios.

Conclusions

According to our data, Anandaraja's formula tends towards an overestimation or underestimation of LDL cholesterol levels, depending on whether the HDL cholesterol levels are high or low, which may be clinically significant. These results do not support the proposed better accuracy of the Anandaraja's than the Friedewald's formula.     

Waist Circumference Provides an Indication of Numerous Cardiometabolic Risk Factors in Adults With Cerebral Palsy

Objective

To report the prevalence of cardiometabolic risk factors in a cohort of adults with cerebral palsy (CP) and to investigate the ability of anthropometric measures to predict these factors.

Design

Cross-sectional study.

Setting

Testing took place in a laboratory setting.

Participants

Adults with CP (N=55; mean age, 37.5±13.3y; Gross Motor Function Classification System levels, I–V) participated in this study.

Interventions

Not applicable.

Main Outcome Measures

Total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, insulin, and C-reactive protein levels were measured from a fasting venous blood sample. Insulin resistance was calculated using the Homeostasis Model Assessment (HOMA-IR) index. Blood pressure, body mass index (BMI), waist circumference (WC), waist-hip ratio, and waist-height ratio were also measured. The metabolic syndrome (MetS) was defined according to the 2009 Joint Interim Statement.

Results

The prevalence of the MetS was 20.5% in ambulatory adults and 28.6% in nonambulatory adults. BMI was associated with HOMA-IR only (β=.451; P<.01). WC was associated with HOMA-IR (β=.480; P<.01), triglycerides (β=.450; P<.01), and systolic blood pressure (β=.352; P<.05). Receiver operating characteristic curve analysis revealed that WC provided the best indication of hypertensive blood pressure, dyslipidemia, HOMA-IR, and the presence of multiple risk factors (area under the curve, .713–.763).

Conclusions

A high prevalence of the MetS was observed in this relatively young sample of adults with CP. WC was a better indicator of a number of risk factors than was BMI and presents as a clinically useful method of screening for cardiometabolic risk among adults with CP.     

Atherogenic lipid profile and high sensitive C-reactive protein in patients with rheumatoid arthritis

Objectives

The objective of this study was to investigate the lipid profile and high sensitive C-reactive protein (hs-CRP) levels in rheumatoid arthritis (RA) patients, and compare them with healthy controls, and also compare the different patterns of these parameters during active RA between male and female patients.

Design and methods

We studied 60 RA patients and 65 controls matched by age and sex. All cases were selected from the Rheumatology Department of a tertiary care hospital, Delhi, India and fulfilled the 1987 American College of Rheumatology revised criteria for RA.

Results

We found that male RA patients had significantly higher levels of hs-CRP (p < 0.001), low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol (HDL-C) (p < 0.001), total cholesterol (TC)/HDL-C (p < 0.05), and lower level of HDL-C (p < 0.01), than male controls. The mean levels of HDL-C and TC were high (p < 0.05), and LDL-C, LDL-C/HDL-C (p < 0.01), and hs-CRP (p < 0.001) were low in healthy females as compared to female RA patients. Between RA patients, females had significantly high level of HDL-C (p < 0.001), and low levels of TC/HDL-C and LDL-C/HDL-C (p < 0.001) as compared to RA males. Mean levels of TC and HDL-C were higher in healthy females (p < 0.05) and triglyceride (TG) was lower (p < 0.05) than in healthy males.

Conclusions

Results demonstrate that the RA patients have high levels of inflammatory marker hs-CRP and altered lipid profile, and these are affected by the gender of the RA patients. Lipid levels should be monitored and managed in patients with RA to minimize the long-term risk of cardiovascular disease.     

Circulating secretory type IIA phospholipase A2, lipoprotein (a) and soluble cellular adhesion molecule levels in patients with angina pectoris

Objectives

To examine the plasma levels of secretory type IIA phospholipase A2 (sPLA₂-IIA), lipoprotein (a) [Lp(a)], soluble intercellular adhesion molecule-1 (sICAM-1) and soluble platelet endothelial CAM-1 (sPECAM-1), as well as ICAM-1 (K469E) and PECAM-1 (Leu125Val) gene polymorphisms, in patients with unstable angina pectoris (UAP) and stable AP (SAP).

Design and methods

We enrolled 75 patients with SAP, 72 with UAP and 80 controls without angina. Blood samples were obtained before angiography.

Results

The concentrations of sPLA₂-IIA, sICAM-1 and sPECAM-1 were higher for UAP patients than for SAP patients and controls, and the level of Lp(a) was higher for UAP patients than for controls. Lp(a) and sPLA₂-IIA levels were significantly correlated, and high plasma Lp(a) level (≥ 300 mg/L) was an independent risk factor for angina.

Conclusion

Lp(a) may play an important role in the development of angina. Further research should investigate the role of sPLA₂-IIA, sICAM-1 and sPECAM-1 in UAP.     

Validation of the Friedewald formula for the determination of low-density lipoprotein cholesterol compared with beta-quantification in a large population

Lipoprotein data from 9477 subjects, covering a wide range of total plasma cholesterol levels, were used to examine the validity of the Friedewald formula for estimating plasma concentrations of low-density lipoprotein cholesterol (LDL-C) using high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) concentrations. Values of LDL-C obtained from the Friedewald formula were compared with values of LDL-C derived from preparative ultracentrifugation used as a reference method. We found that the bias associated with the Friedewald formula was not related to plasma LDL-C levels and was smaller than −4.0% even for plasma LDL-C values <3.0 mmol/l. Moreover, in the subgroup of individuals with plasma TG levels ≤4.5 mmol/l, the Friedewald formula underestimated LDL-C levels with a bias between −3.1% and −1.9% according to TG quartiles. Interestingly, the Friedewald formula showed no significant bias in patients with plasma TG levels between 4.51 and 8.82 mmol/l, suggesting that the calculated LDL-C are reliable and could be clinically useful in patients with plasma TG levels higher than 4.5 mmol/l which is the reference cut-point value used by most clinical laboratories. Finally, multiple regression analyses showed that the very low-density lipoprotein cholesterol (VLDL-C)/TG ratio represented nearly 63% (P < 0.0001) of the variance of the bias associated with the Friedewald formula. We concluded that the Friedewald formula may be reliable at low LDL-C levels and at TG levels up to 9 mmol/l but may be used with caution when the VLDL-C/TG ratio is high as observed in patients with type III dysbetalipoproteinemia.     

Atorvastatin in stable angina patients lowers CCL2 and ICAM1 expression: Pleiotropic evidence from plasma mRNA analyses

Objective

Statin pleiotropy is still an evolving concept, and the lack of clarity on this subject is due at least in part to the lack of a definitive biomarker for statin pleiotropy. Using plasma mRNA analysis as a novel research tool for the non-invasive in vivo assessment of gene expression in vascular beds, we hypothesised that atorvastatin lowers the plasma mRNA level from statin pleiotropy-target genes, and the reduction is independent of the reduction of low-density lipoprotein cholesterol (LDL-C).

Design and methods

Forty-four patients with stable angina received atorvastatin therapy (20 mg/day, 10 weeks). Plasma chemokine (C-C motif) ligand 2 (CCL2) and intercellular adhesion molecule-1 (ICAM1) mRNA levels and their protein concentrations (MCP-1, sICAM-1) were analysed before and after the treatment. Plasma vascular adhesion molecule-1 (sVCAM-1) concentrations were also analysed.

Results

Atorvastatin lowered plasma mRNA levels (CCL2: − 31.76%, p = 0.037; ICAM1: − 34.09%, p < 0.001) and MCP-1 protein concentration (− 18.88%, p = 0.008) but did not lower sICAM-1 and sVCAM-1 protein concentrations, and the decreases appeared to be independent from the lowering of LDL-C. The plasma mRNA levels correlated with their protein concentrations following statin treatment only.

Conclusion

Our results significantly strengthen the clinical evidence in support of statin pleiotropy. Furthermore, this unique simultaneous measurement of plasma mRNAs and their protein concentrations offers an advanced non-invasive in vivo assessment of the circulation pathology.     

New LDL-Cholesterol Lowering Therapies: Pharmacology,Clinical Trials,and Relevance to Acute Coronary Syndromes

Background

Reduction in plasma low-density lipoprotein cholesterol (LDL-C) is a fundamental treatment for the prevention of acute coronary syndromes (ACS). Although statin therapy confers significant protection against ACS in both primary and secondary prevention, a considerable residual risk remains after intensive therapy. In addition, a significant proportion of high-risk patients do not achieve the optimal LDL-C goal recommended in the current guidelines (<1.8 mmol/L). Hence, novel LDL-C-lowering agents that act via mechanisms distinct from HMG-CoA reductase inhibition are under investigation.

Objective

We reviewed the recent literature on the development of novel LDL-C–lowering agents that could potentially be used as an alternative or adjunct to statin therapy in high-risk coronary patients.

Methods

PubMed and Scopus databases were searched to retrieve studies on the efficacy and/or tolerability of novel LDL-C-lowering agents in animals and humans.

Results

Agents that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein (apo) B, and microsomal triglyceride transfer protein (MTTP) are the most promising therapies. Inhibition of PCSK9, apoB, and MTTP has been achieved mostly via fully humanized monoclonal antibodies (mAbs), antisense oligonucleotides, and synthetic compounds, respectively. PCSK9 inhibitors increase the hepatic uptake of LDL-C, while apoB and MTTP inhibitors decrease the synthesis and secretion of apoB-containing lipoproteins. These 3 mechanisms lead to marked reductions in plasma LDL-C in patients with hypercholesterolemia at risk for ACS, particularly those with familial hypercholesterolemia. Moreover, these agents can exert additional benefits by decreasing plasma levels of apoB, triglycerides, and lipoprotein(a). Mipomersen and lomitapide have been approved by the United States Food and Drug Administration (US FDA) for use in patients with homozygous familial hypercholesterolemia. PCSK9 inhibitors are currently under final evaluation in clinical outcomes studies and are anticipated to find wide application either as monotherapy or as an adjunct to statins. A main safety concern is the risk for hepatic steatosis with apoB and MTTP inhibitors, which needs to be explored in prospective, long-term trials.

Conclusions

PCSK9, apoB, and MTTP inhibitors can exert potent reductions in plasma LDL-C and apoB concentrations, either as monotherapy or in combination with statins. These effects are particularly relevant to high-risk individuals with marked hypercholesterolemia, such as those with familial hypercholesterolemia. Although the use of mipomersen and lomitapide is limited to severe familial hypercholesterolemia as a replacement for LDL-apheresis, PCSK9 inhibitors are likely to be more widely prescribed in patients at high risk for CVD, especially those who are resistant to or intolerant of high-intensity statin therapy. PCSK9 mAbs are efficacious and have an excellent safety profile, but their long-term impact on cardiovascular events is currently under investigation. Whether PCSK9 mAbs decrease the rates of recurrent cardiovascular events within 3 months following ACS is questionable; however, these agents, unlike statins, may not have pleiotropic benefits on the unstable plaque.     

Relationship between apo(a) length polymorphism and lipoprotein(a) concentration in healthy Ivorian subjects with single or double apo(a) isoforms

Objectives

To determine the relationship between apo(a) size and Lp(a) concentration in healthy Ivorian subjects.

Methods

Serum Lp(a) was measured by immunonephelometry and electroimmunodiffusion, and apo(a) size determined by immunoblotting.

Results

Both assay methods provided comparable information. Lp(a) concentrations showed a non-Gaussian distribution and skewed towards higher values. Apo(a) isoform size distribution exhibited three frequency peaks at 18, 22 and 25 kringles. Single and double apo(a) isoforms were detected in 36% and 64% of subjects, respectively. Lp(a) values were higher in subjects with double isoforms, the major isoform being of lower size. An inverse correlation between apo(a) size and Lp(a) concentration was found, apo(a) size accounting for more than 30% of Lp(a) concentration in “single-band” group, whereas being weaker in “double-band” group. Low size isoforms were associated with higher Lp(a) concentrations, high size isoforms with higher variability.

Conclusions

Lp(a) concentrations were inversely correlated to apo(a) size. This study has shown the relationship between apo(a) size and Lp(a), the influence of apo(a) size varying according to the phenotype. Apo(a) “double isoform” phenotype confers elevated levels to Lp(a) in healthy Ivorian subject.     

Are patients with hyperlipidemia undertreated?: Study of patients admitted to hospital with coronary events

OBJECTIVE

To identify patients admitted to hospital with coronary events and to estimate their pre-admission coronary risk, including their lipid levels. Despite the available data and numerous guidelines, evidence indicates that many patients with hyperlipidemia are undertreated and are not achieving target lipid levels.

DESIGN

Retrospective chart review.

SETTING

Acute care community hospital in Winnipeg, Man.

PARTICIPANTS

A total of 153 patients who were diagnosed with acute myocardial infarction, unstable angina, or acute coronary syndrome upon admission.

METHOD

Each patient’s 10-year risk of developing coronary artery disease was calculated, and his or her risk status was established. Each patient’s low-density lipoprotein cholesterol (LDL-C) levels were recorded and categorized based on current Canadian guidelines.

RESULTS

Mean age of patients was 67.6 years; 60.8% were male. Patients in the low-risk category had a mean LDL-C level of 2.98 mmol/L (95% confidence interval [CI] 2.66 to 3.29), and patients in the moderate-risk category had a mean LDL-C level of 3.01 mmol/L (95% CI 2.74 to 3.28), both significantly lower (P < .05) than the LDL-C target levels for patients in those risk categories according to Canadian guidelines. The mean LDL-C level for patients in the very high-risk category, however, was 2.53 mmol/L (95% CI 2.35 to 2.71), above the recommended goal. Almost half the patients (48.3%) in thevery high-risk category had LDL-C levels that exceeded the goal. Slightly more than 1 in 3 patients in the very high-risk category was reported to be taking lipid-lowering agents.

CONCLUSION

Patients in the community who are at very high risk of havingcardiovascular events are undertreated with respect to attaining LDL-C target levels. These findings point to an opportunity to prevent patient morbidity and reduce the number of hospitalizations for cardiovascular events.     

Serum lipid profile,cytokine production,and clinical outcome in patients with severe sepsis

Purpose

The purpose of the study is to evaluate the prevalence and clinical significance of hypolipidemia and the relationship to cytokine concentrations and outcomes in septic patients.

Materials and methods

A prospective study was undertaken including 50 patients with severe sepsis due to community-acquired infections. Serum concentrations of total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein as well as tumor necrosis factor α (TNF-α), interleukin (IL) 6, IL-8, IL-10, and transforming growth factor (TGF) β₁ were determined on admission and days 3 and 10 during hospitalization.

Results

Of the 50 patients enrolled, 28 survived, whereas 22 died during their hospital stay. Sepsis survivors had significantly higher HDL-C concentrations than nonsurvivors, whereas all patients with HDL-C values greater than 25 mg/dL survived. Baseline levels of TGF-β₁ were significantly higher in survivors. High-density lipoprotein levels correlated inversely with TNF-α, IL-6, and IL-10 concentrations and positively with baseline TGF-β₁ levels. Independent risk factors of mortality were IL-10 levels on day 3, whereas HDL-C concentration on admission was related to survival.

Conclusions

Low cholesterol and lipoprotein concentrations are detected in septic patients, especially in individuals with poor outcome. High-density lipoprotein cholesterol concentration seems to be an early independent predictive marker of survival in severe sepsis.