Target Of Lipid-lowering Therapy Research Articles

Ceramides improve cardiovascular risk prediction beyond low-density lipoprotein cholesterol.

Low-density lipoprotein cholesterol (LDL-C) is the best documented cardiovascular risk predictor and at the same time serves as a target for lipid-lowering therapy. However, the power of LDL-C to predict risk is biased by advanced age, comorbidities, and medical treatment, all known to impact cholesterol levels. Consequently, such biased patient cohorts often feature a U-shaped or inverse association between LDL-C and cardiovascular or overall mortality. It is not clear whether these constraints for risk prediction may likewise apply to other lipid risk markers in particular to ceramides and phosphatidylcholines. In this observational cohort study, we recorded cardiovascular mortality in 1195 patients over a period of up to 16 years, comprising a total of 12 262 patient-years. The median age of patients at baseline was 67 years. All participants were either consecutively referred to elective coronary angiography or diagnosed with peripheral artery disease, indicating a high cardiovascular risk. At baseline, 51% of the patients were under statin therapy. We found a U-shaped association between LDL-C and cardiovascular mortality with a trough level of around 150 mg/dL of LDL-C. Cox regression analyses revealed that LDL-C and other cholesterol species failed to predict cardiovascular risk. In contrast, no U-shaped but linear association was found for ceramide- and phosphatidylcholine-containing markers and these markers were able to significantly predict the cardiovascular risk even after multivariate adjustment. We thus suggest that ceramides- and phosphatidylcholine-based predictors rather than LDL-C may be used for a more accurate cardiovascular risk prediction in high-risk patients.

Non-HDL-cholesterol is a better marker of atherogenic dyslipidemia in obstructive sleep apnea

Background and Aims : Obstructive sleep apnea (OSA) is independently associated with dyslipidemia. LDL-cholesterol is accepted as a major independent risk factor for cardiovascular disease. However, non-HDL-cholesterol is a better marker of atherogenic dyslipidemia and recommended as a target of lipid lowering therapy. We aimed to assess the prevalence of atherogenic dyslipidemia, and relationship between OSA severity and serum LDL-cholesterol and non-HDL cholesterol levels in OSA patients.

Could non-HDL-cholesterol be a better marker of atherogenic dyslipidemia in obstructive sleep apnea?

Background/objectiveObstructive sleep apnea (OSA) is independently associated with dyslipidemia, a surrogate marker of atherosclerosis. Low-density lipoprotein (LDL)-cholesterol is accepted as a major independent risk factor for cardiovascular disease. However, non-high-density lipoprotein (HDL)-cholesterol is a better marker of atherogenic dyslipidemia and recommended as a target of lipid lowering therapy. We aimed to assess the prevalence of atherogenic dyslipidemia, and relationship between OSA severity and serum LDL-cholesterol and non-HDL cholesterol levels in OSA patients. MethodsWe retrospectively evaluated treatment naïve 2361 subjects admitted to the sleep laboratory of a university hospital for polysomnography. All subjects’ lipid profile including total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and non-HDL-cholesterol were measured. ResultsOut of 2361 patients (mean age 49.6 ± 11.9 years; 68.9% male, apnea-hypopnea index 36.6 ± 28.4/h), 185 (7.8%) had no OSA and 2176 (92.2%) had OSA. Atherogenic dyslipidemia prevalence was high (57–66%) in OSA patients, and especially increased in severe OSA compared to other groups (p < 0.05). Though total and LDL-cholesterol did not differ between those with and without OSA, non-HDL-cholesterol (p = 0.020), and triglycerides (p = 0.001) were higher and HDL-cholesterol levels (p = 0.018) were lower in OSA patients than non-OSA. Non-HDL-cholesterol was significantly correlated with OSA severity (p < 0.001) and hypoxia parameters (p < 0.01), whereas LDL-cholesterol showed no correlation. ConclusionsAtherogenic dyslipidemia is highly prevalent and non-HDL-cholesterol levels are significantly increased, predominantly in severe OSA patients. Non-HDL-cholesterol but not LDL-cholesterol, is significantly correlated with OSA severity and hypoxia parameters. Therefore, it could be better to use non-HDL-cholesterol, which is a guideline recommended target of lipid therapy, as a marker of atherosclerotic cardiovascular risk in OSA patients.

Circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) are associated with monocyte subsets in patients with stable coronary artery disease

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): FWF Background and aims Proprotein convertase subtilisin/kexin type-9 (PCSK9) is an enzyme promoting the degradation of low-density lipoprotein receptors (LDL-R) in hepatocytes. Inhibition of PCSK9 has emerged as a novel target for lipid-lowering therapy. Monocytes are crucially involved in the pathogenesis of atherosclerosis and can be divided into three subsets. The aim of this study was to examine whether circulating levels of PCSK9 are associated with monocyte subsets. Methods We included 69 patients with stable coronary artery disease. PCSK9 levels were measured and monocyte subsets were assessed by flow cytometry and divided into classical monocytes (CD14++CD16-; CM), intermediate monocytes (CD14++CD16+; IM) and non-classical monocytes (CD14 + CD16++; NCM). Results Mean age was 64 years and 80% of patients were male. Patients on statin treatment (n = 55) showed higher PCSK9-levels (245.4 (206.0-305.5) ng/mL) as opposed to those without statin treatment (186.1 (162.3-275.4) ng/mL; p = 0.05). In patients on statin treatment, CM correlated with circulating PCSK9 levels (R = 0.29; p = 0.04), while NCM showed an inverse correlation with PCSK9 levels (R=-0.33; p = 0.02). Patients with PCSK9 levels above the median showed a significantly higher proportion of CM as compared to patients with PCSK-9 below the median (83.5 IQR 79.2-86.7 vs. 80.4, IQR 76.5-85.2%; p = 0.05). Conversely, PCSK9 levels &amp;gt;median were associated with a significantly lower proportion of NCM as compared to those with PCSK9 &amp;lt;median (10.2, IQR 7.3-14.6 vs. 14.3, IQR 10.9-18.7%; p = 0.02). In contrast, IM showed no association with PCSK-9 levels. Conclusions We hereby provide a novel link between PCSK9 regulation, innate immunity and atherosclerotic disease in statin-treated patients.

Circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) are associated with monocyte subsets in patients with stable coronary artery disease

BackgroundProprotein convertase subtilisin/kexin type-9 (PCSK9) is an enzyme promoting the degradation of low-density lipoprotein receptors (LDL-R) in hepatocytes. Inhibition of PCSK9 has emerged as a novel target for lipid-lowering therapy. Monocytes are crucially involved in the pathogenesis of atherosclerosis and can be divided into three subsets. ObjectiveThe aim of this study was to examine whether circulating levels of PCSK9 are associated with monocyte subsets. MethodsWe included 69 patients with stable coronary artery disease. PCSK9 levels were measured and monocyte subsets were assessed by flow cytometry and divided into classical monocytes (CD14++CD16-; CM), intermediate monocytes (CD14++CD16+; IM) and non-classical monocytes (CD14+CD16++; NCM). ResultsMean age was 64 years and 80% of patients were male. Patients on statin treatment (n = 55) showed higher PCSK9-levels (245.4 (206.0–305.5) ng/mL) as opposed to those without statin treatment (186.1 (162.3–275.4) ng/mL; p = 0.05). In patients on statin treatment, CM correlated with circulating PCSK9 levels (R = 0.29; p = 0.04), while NCM showed an inverse correlation with PCSK9 levels (R = -0.33; p = 0.02). Patients with PCSK9 levels above the median showed a significantly higher proportion of CM as compared to patients with PCSK9 below the median (83.5 IQR 79.2–86.7 vs. 80.4, IQR 76.5–85.2%; p = 0.05). Conversely, PCSK9 levels >median were associated with a significantly lower proportion of NCM as compared to those with PCSK9 <median (10.2, IQR 7.3-14.6 vs. 14.3, IQR 10.9–18.7%; p = 0.02). In contrast, IM showed no association with PCSK9 levels. ConclusionsWe hereby provide a novel link between PCSK9 regulation, innate immunity and atherosclerotic disease in statin-treated patients.

Stability of serum biochemical markers during standard long-term storage and with a single thawing

Aim. To study the effect of standard serum long-term storage at -70О C and with a single thawing on the biochemical markers by comparing the results of studies carried out in 2013-2014 and 2020.Material and methods. The material was the blood serum of participants in the ESSE-RF study, which was stored in a specialized biobank from 2013-2014 at -70О C either continuously (n=149) or with a single thawing (n=20). Initially and in 2020, the quantitative determination of serum biochemical parameters was carried out using same equipment and standard techniques.Results. Long-term storage at -70О C led to mild, but significant changes in almost all analyzed parameters: low density lipoprotein cholesterol (LDL-C) and apolipoprotein A1 levels decreased; levels of highdensity lipoprotein cholesterol (HDL-C), triglycerides, apolipoprotein B, glucose, and high-sensitivity C-reactive protein increased. Insulin and thyroid-stimulating hormone levels did not change during storage. The revealed strong positive relationships between the initial concentrations and those measured in 2020 in samples that were stored continuously indicate the relevance of such storage. In samples with single thawing, changes in most parameters were more pronounced.Conclusion. The results of a prospective cohort study aimed at studying the stability of human serum samples during storage indicate the validity of long-term storage at -70О C without thawing. Freeze-thawing cycle of samples (even once) is unacceptable, since it leads to a pronounced LDL-C decrease. Given the fact that it is the LDL-C levels that is the target of lipid-lowering therapy, continuous low-temperature (not &gt;-70О C) storage of blood serum samples is recommended.

Abstract 15930: Circulating Levels of Proprotein Convertase Subtilisin/kexin Type 9 (pcsk9) are Associated With Monocyte Subsets in Patients With Stable Coronary Artery Disease

Introduction: Proprotein convertase subtilisin/kexin type-9 (PCSK9) is an enzyme promoting the degradation of low-density lipoprotein receptors (LDL-R) in hepatocytes. Inhibition of PCSK9 has emerged as a novel target for lipid-lowering therapy. Monocytes are crucially involved in the pathogenesis of atherosclerosis. Circulating monocytes can be divided into three subsets. The aim of this study was to examine whether circulating levels of PCSK9 are associated with monocyte subsets. Methods: We included 69 patients with stable coronary artery disease. PCSK9 levels were measured and monocyte subsets were assessed by flow cytometry and divided into classical monocytes (CD14++CD16-; CM), intermediate monocytes (CD14++CD16+; IM) and non-classical monocytes (CD14+CD16++; NCM). Results: Mean age was 64 years and 80% of patients were male. Patients on statin treatment (n=55) showed higher PCSK9-levels (245.4 (206.0-305.5) ng/mL) as opposed to those without statin treatment (186.1 (162.3-275.4) ng/mL; p=0.05). In patients on statin treatment, CM correlated with circulating PCSK9 levels (R=0.29; p=0.04), while NCM showed an inverse correlation with PCSK9 levels (R=-0.33; p=0.02). Patients with PCSK9 levels above the median showed a significantly higher proportion of CM as compared to patients with PCSK-9 below the median (83.5 IQR 79.2-86.7 vs. 80.4, IQR 76.5-85.2%; p=0.05). Conversely, patients with PCSK9 levels &gt;median were associated with a significantly lower proportion of NCM as compared to those with PCSK9 &lt;median (10.2, IQR 7.3-14.6 vs. 14.3, IQR 10.9-18.7%; p=0.02). In contrast, IM showed no association with PCSK-9 levels. Conclusions: We hereby provide a novel link between PCSK9 regulation, innate immunity and atherosclerotic disease in statin-treated patients.

Comparison of LDL-C calculation by friedewald and martin/hopkins methods in 12,243 adults from the United States of America

Abstract Background Low-density lipoprotein cholesterol (LDL-C) is an established risk factor for cardiovascular disease (CVD), and a target for lipid-lowering therapy. LDL-C is typically not measured directly but is estimated using the Friedewald formula, which assumes a fixed factor for the ratio of triglycerides (TG) to very low-density lipoprotein cholesterol (VLDL-C). However this assumption is sometimes not valid. The Martin/Hopkins (M/H) formula estimates LDL-C using an adjustable factor for the TG:VLDL-C ratio and is expected to improve upon Friedewald when predicting measured LDL-C, and apolipoprotein B (ApoB), one molecule of which is associated with each LDL particle. Purpose We compared values of LDL-C calculated by the Friedewald and M/H methods with respect to their correlation with non-high density lipoprotein cholesterol (non-HDL-C) and ApoB, and their classification of individuals based upon attainment of the threshold value of 70 mg/dl (1.8 mmol/l) of LDL-C. This cut-point is a treatment target for individuals at high risk of CVD in the 2019 ESC guidelines for lipid modification, and a threshold for initiating statin therapy in the 2019 ACC/AHA guidelines. Methods In this analysis we included participants in the National Health and Nutrition Examination Survey (NHANES) from 2005–2016, age ≥18, &amp;lt;80 years who had measurements for total cholesterol (TC), TG and HDL-C. LDL-C was calculated using Friedewald and M/H. We correlated LDL-C (calculated using the two methods) with non-HDL-C and ApoB. We identified individuals with LDL-C &amp;lt;70 mg/dl using both methods. When LDL-C (Friedewald) was &amp;lt;70, but LDL-C (M/H) was &amp;gt;70, we classified these participants as discordant. Statistical analyses were performed in IBM SPSS for Windows v26. Results 12,243 individuals were included. 51.8% were female, mean (±SD) age was 45.5±17.4, 15.3% were treated with statins, ApoB was available for 2179 participants. Mean lipid concentrations (mg/dl) were: TC: 191.5±41.0, TG: 120.0±67.0, HDL-C: 54.1±15.7, LDL-C (Friedewald): 113.3±35.4; LDL-C (M/H): 114.9±35.2. In the whole population, LDL-C (M/H) was more strongly correlated than LDL-C (Friedewald) with ApoB (r=0.935 v 0.894) and non-HDL-C (r=0.981 v 0.944). In statin-treated participants, LDL-C (M/H) was also more strongly correlated with ApoB (r=0.951 v 0.914) and non-HDL-C (r=0.979 v 0.928). 1139 participants had LDL-C (Friedewald) &amp;lt;70 mg/dl. Of these, 206 individuals (18.1%) were discordant, having LDL-C (M/H) &amp;gt;70 mg/dl. Amongst statin-treated patients, 22.9% were discordant. Only 5.5% of individuals with LDL-C (M/H) &amp;lt;70 mg/dl showed reverse discordance (LDL-C (Friedewald) &amp;gt;70 mg/dl). Conclusions The M/H method of calculating LDL-C correlates more strongly with non-HDL-C and ApoB than Friedewald. Importantly the discordant results confirm previous observations that Friedewald underestimates LDL-C at low concentrations. This may result in under-use of lipid-lowering therapies. Funding Acknowledgement Type of funding source: None

ACHIEVEMENT OF NEW EUROPEAN DYSLIPIDEMIA-GUIDELINE LOW-DENSITY LIPOPROTEIN CHOLESTEROL TREATMENT GOALS AFTER ACUTE CORONARY SYNDROME: INSIGHTS FROM ODYSSEY OUTCOMES

The 2019 European Society of Cardiology/European Atherosclerosis Society dyslipidemia guidelines have recalibrated targets of lipid-lowering therapy, particularly for secondary prevention. In patients (pts) with coronary heart disease considered very high risk, a low-density lipoprotein cholesterol

Clinical review on triglycerides.

Hypertriglyceridaemia is a common clinical problem. Epidemiologic and genetic studies have established that triglyceride-rich lipoproteins (TRL) and their remnants as important contributors to ASCVD while severe hypertriglyceridaemia raises risk of pancreatitis. While low-density lipoprotein is the primary treatment target for lipid lowering therapy, secondary targets that reflect the contribution of TRL such as apoB and non-HDL-C are recommended in the current guidelines. Reduction of severely elevated triglycerides is important to avert or reduce the risk of pancreatitis. Here we discuss interventions for hypertriglyceridaemia, including diet and lifestyle, established treatments such as fibrates and omega-3 fatty acid preparations and emerging therapies, including various biological agents.

Fixeddose combination of rosuvastatin + ezetimibe: ease of use, safety and efficacy

Today, cardiovascular diseases remain the leading cause of morbidity and mortality globally. Hyperlipidemia and dyslipidemia are key points in the occurrence and progression of CVDs, as well as the development of its complications. Elevated low density lipoprotein cholesterol (LDL-C) is the target of lipid-lowering therapy. The LDL-C target level is often not achieved in everyday clinical practice, which is especially important for patients at high and very high risk for cardiovascular complications. Furthermore, in some patient subgroups, atherogenic dyslipidemia is observed. Due to use of intensive and prolonged lipid-lowering therapy, the problem of its tolerability and patient adherence to the treatment becomes a live issue today. In addition, the use of drugs with effect that complements and enhances the effect of statin helps to achieve targets and improve long-term prognosis. Statins and ezetimibe are effective and widely used drugs to treat dyslipidemia. Clinical studies show that ezetimibe can be safely co-administered with statins to enhance lipid-lowering activity. In this regard, a statin and non-statin drug fixed-dose combination tablet may have additional advantages both for enhancing the lipidlowering effect and for greater patient convenience. Rosuvastatin is more effective than other statins in reducing low density lipoprotein cholesterol. The article provides a rationale for the possibility, efficacy, safety and convenience of using an ezetimibe and rosuvastatin fixed-dose combination tablet in patients with a high and very high risk and unattained target level of low density lipoprotein cholesterol.

ATHEROGENIC INDEX OF PLASMA IS A MARKER OF PLAQUE VULNERABILITY IN CORONARY ARTERY DISEASE

SESSION TITLE: Cardiovascular Disease Outcomes SESSION TYPE: Original Investigations PRESENTED ON: 10/09/2018 10:45 AM - 11:45 AM PURPOSE: Atherogenic index of plasma (AIP) is defined as the logarithmic ratio of molar concentrations of triglyceride & high-density lipoprotein. AIP correlates closely with the LDL particle size. Atherosclerosis is a systemic, lipid-driven immune-inflammatory state. We used AIP & neutrophil-lymphocyte ratio (NLR) as surrogate markers of plasma atherogenicity & inflammation. In this study, we sought to determine if AIP & NLR can reflect the lipid-driven inflammatory state in acute coronary syndrome. METHODS: A retrospective chart review of 390 patients who underwent cardiac catheterization from January to March 2016 was done. 77 patients with prior history of PCI & CABG were excluded. Patients were divided into acute coronary syndrome (ACS) & non-ACS group based on the indication for cardiac catheterization. ACS group was regarded as study group & non-ACS group was regarded as the control group. Data pertaining to demographics, lipid profile including total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) & low-density lipoprotein (LDL) were recorded. AIP was calculated using log (TG/HDL) ratio. Neutrophil: Lymphocyte ratio (NLR) was calculated using simple arithmetic ratio. All the variables were compared in between the study & control groups. Results in the two groups were statistically tested using the chi-squared test. RESULTS: A total of 313 patients mean age (62.98 ± 11.54 years, 54% male & 46% female) were included in the study. 189 patients were categorized in the ACS group & 124 patients in the non-ACS group. Distribution of risk factors was similar in both groups. Mean age (p=0.13) was 63.64 ± 12.63 & 62.24 ±12.79 in non-ACS & ACS groups. TC: HDL ratio (p=0.07) was higher in ACS group; 3.64 ± 0.37 compared to 3.46 ± 0.49 in non-ACS group. Atherogenic Index of plasma (AIP); (p=0.01) was high in ACS group measuring 0.39 ± 0.03 compared to 0.35 ± 0.02 in non-ACS group. Neutrophil-lymphocyte ratio (NLR); (p=0.02) measured 2.81 ± 0.23 in ACS group compared to 2.55 ± 0.19 in the non-ACS group. CONCLUSIONS: High AIP & NLR potentially reflects the lipid-driven inflammatory state in acute coronary syndrome. This also suggests lipid-driven inflammatory process as a possible mechanism for plaque vulnerability. AIP can be easily calculated from the standard lipid profile & it can potentially add predictive value for future cardiovascular risk. Atherogenic index of plasma can be used as a target for lipid-lowering therapy beyond individual lipoprotein and/or TC: HDL ratio. CLINICAL IMPLICATIONS: Atherogenic index of plasma can potentially serve as a marker for high-risk atherosclerotic coronary artery disease. It can be used as a target for lipid-lowering therapy beyond individual lipoprotein and/or TC: HDL ratio. DISCLOSURES: No relevant relationships by Soney Basnyat, source=Web Response No relevant relationships by Surjeet Dheer, source=Web Response No relevant relationships by Reshma Golamari, source=Web Response No relevant relationships by Sonul Gulati, source=Web Response no disclosure on file for Ajay Koirala; no disclosure on file for Prasad Konda; no disclosure on file for Paritosh Prasai; No relevant relationships by Munis Raza, source=Web Response No relevant relationships by Yub Raj Sedhai, source=Web Response No relevant relationships by Subtain Zia, source=Web Response

Serum Levels of PCSK9 Are Associated with Coronary Angiographic Severity in Patients with Acute Coronary Syndrome.

BackgroundProprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that promotes degradation of the low density lipoprotein receptor. PCSK9 has emerged as a target for lipid-lowering therapy, but the predictive value of the serum level of PCSK9 for the severity of coronary disease is largely unknown.MethodsFrom December 2009 to July 2012, 121 individuals who underwent coronary angiography (CAG) because of clinically suspected acute coronary syndrome were enrolled in this study. Serum levels of PCSK9 and metabolic parameters were measured. SYNTAX (SYNergy between percutaneous coronary intervention with [paclitaxel-eluting] TAXUS stent and cardiac surgery) and GRACE (Global Registry of Acute Coronary Events) scores were calculated.ResultsIndividuals with CAG lesions (n=100) had significantly higher levels of PCSK9 than those without lesions (n=21). The study population was stratified into three groups according to serum levels of PCSK9. The odds radio for occurrence of one or more CAG lesions was significantly higher in the group with the highest level of PCSK9 (odds ratio, 7.468; P=0.011) than in the group with the lowest level of PCSK9. Serum PCSK9 was positively associated with the number of involved coronary arteries. Multivariable linear regression indicated that levels of PCSK9 were positively correlated with GRACE risk scores and SYNTAX scores.ConclusionSerum PCSK9 concentrations are higher in patients with coronary artery lesions, and are associated with SYNTAX and GRACE scores, suggesting that PCSK9 is a potential biomarker of the severity of coronary artery disease.

PCSK9: BIOLOGICAL ACTIVITY REGULATION AND CONNECTION WITH LIPID AND CARBOHYDRATE METABOLISM

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease which plays an important role in the regulation of LDL receptor (LDLR) expression and apolipoprotein B (apoB) lipoprotein cholesterol metabolism. It is well known that hepatic PCSK9 expression, its activity and secretion influence cholesterol homeostasis. An upregulation of PCSK9 causes an increase of LDLR degradation, which results in decrease of apoB lipoprotein uptake, and a consequent increase in plasma lipoprotein concentration, including LDL. Therefore, PCSK9 has become a new target for lipid lowering therapy. The aim of this review is to consider current data on metabolic and dietary regulation of PCSK9 and its effect on cholesterol and apoB lipoproteins metabolism and risk of cardiovascular disease.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) level in patients with familial hypercholesterolemia in Russia

Aim: Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates the amount of LDL receptors and plasma cholesterol concentrations, it’s new target for lipid lowering therapy and perspective biomarker for predicting cardiovascular events based on some resent data. The aim was to investigate the association of the PCSK9 protein with lipid parameters, carotid artery intima-media thickness in patients with familial hypercholesterolemia (FH).

Apolipoprotein B vs non–high-density lipoprotein cholesterol: Association with endothelial hemostatic markers and carotid intima-media thickness

Both apolipoprotein B (apoB) and non-high-density lipoprotein cholesterol (non-HDL-C) are accepted as alternative risk factors or targets for lipid-lowering therapy, which correlate more strongly with cardiovascular events than low-density lipoprotein cholesterol. The aim of this cross-sectional study was to evaluate the differences in plasma levels of plasminogen activator inhibitor-1 (PAI-1) and of von Willebrand factor (vWF) as endothelial hemostatic markers and carotid intima-media thickness (C-IMT) as a morphologic marker for atherosclerotic vascular disease among dyslipidemic individuals with apoB levels higher, estimated or lower based on regression equation of apoB vs non-HDL-C. A total of 594 dyslipidemic subjects without atherosclerotic manifestation were divided into 3 groups (according to tertiles of apoB levels above, within, and below the line of identity): H-apoB (n=200), E-apoB (n=194), and L-apoB (n=200). PAI-1, vWF, C-IMT and lipids, anthropometric parameters, markers of insulin resistance, and inflammation were measured. Differences in variables between groups were analyzed using analysis of variance. There was a strong association between apoB and non-HDL-C. The correlations of apoB and of non-HDL-C with markers of endothelial damage and C-IMT were very similar. Despite these facts, individuals with higher apoB levels had significantly higher levels of PAI-1 compared with individuals with estimated (P<.05) or lower apoB (P<.001). There were no significant differences in vWF, C-IMT, markers of insulin resistance, obesity, and inflammation. Individuals with apoB higher than predicted by non-HDL-C had significantly higher levels of PAI-1, which may contribute to the increased risk of future atherothrombotic events.

Low density lipoprotein cholesterol reduction for the prevention of cardiovascular disease: Newer concepts

Low density lipoprotein cholesterol (LDL-C) is the target of lipid lowering therapy in subjects who have atherosclerotic cardiovascular disease (ASCVD) or who are at risk of developing it. There have been many debatable issues in this field. Should lifelong statins be prescribed for subjects at low risk of ASCVD in primary prevention? How low one can go in LDL-C lowering and is it safe? Should we treat to target or just administer high or moderate or low intensity statins based on the risk category? What is the role of nonstatin drugs in lipid lowering therapy? Are proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9 inhibitors) going to be the game changers? There is an abundance of literature looking at these matters. Statins continue to be the first choice in dyslipidemia management. PCSK9 inhibitors would be a welcome addition to the armamentarium or an attractive alternative in certain situations.

Non-HDL Cholesterol Versus LDL Cholesterol as a CVD Risk Factor in Diabetic Subjects

Objective: Serum low density lipoprotein (LDL) cholesterol is considered as the primary target of lipid lowering therapy and non-high density lipoprotein (HDL) cholesterol is the recommended second target. Recent studies claimed that non-HDL cholesterol is a better predictor of cardiovascular diseases (CVD) than LDL cholesterol. In this study we aimed to compare non-HDL cholesterol and LDL cholesterol as a CVD risk factor in confirmed diabetic subjects. Materials and methods: In this cross-sectional observational study, 1042 confirmed diabetic subjects selected randomly were included. HbA1cResults: In the total subjects, 767 (74%) subjects had LDL cholesterol &gt; 100 mg/dL and 822 (79%) subjects had non- HDL cholesterol &gt; 130 mg/dL. HbA1c values were different (p&lt;0.02) in five groups and showed upward trend (p&lt;0.01). All the lipid parameters studied were significantly different in five groups (p&lt;0.0001) and TC, TG and non-HDL cholesterol showed upward trend (p&lt;0.0001), but HDL cholesterol and LDL cholesterol showed downward trend (p&lt;0.0001). Odds ratio (OR) of likelihood of risk individuals regarding non-HDL cholesterol compared to LDL cholesterol were 0.50 (p&lt;0.001), 1.32 (p&gt;0.05), 2.96 (p&lt;0.001), 6.49 (p&lt;0.001) and 9.37 (p&lt;0.001) for TG concentrations of up to 150 mg/dL, 151-200 mg/dL, 201-250 mg/dL, 251-300 mg/dL and 301-400 mg/dL respectively with relative risk of 0.60, 1.24, 2.43, 4.83, 5.10. Conclusion: LDL cholesterol is a better tool for the detection of high-risk individuals than non-HDL cholesterol at TG concentration up to 150 mg/dL, whereas non-HDL cholesterol is better than LDL cholesterol at TG concentration above 200 mg/dL as a CVD risk factor. DOI: http://dx.doi.org/10.3329/jbcps.v31i4.21004 J Bangladesh Coll Phys Surg 2013; 31: 199-203

Progress in genetic association studies of plasma lipids

Purpose of reviewThis review summarizes recently published large-scale efforts elucidating the genetic architecture of lipid levels. A supplemental file with all genetic loci is provided for research purposes and we performed bioinformatic analyses of the genetic variants to give an oversight of involved pathways.Recent findingsIn total, 52 genes for HDL cholesterol, 42 genes for LDL cholesterol, 59 genes for total cholesterol, and 39 genes for triglycerides have been identified. Genetic overlap is present between the different traits and similar pathways are involved. Most of the SNPs that were detected in the European studies could be replicated in other ethnicities and these SNPs show the same direction of effect suggesting that the underlying genetic architecture of blood lipids is similar between ethnicities.SummaryGenetic studies have identified many loci associated with plasma lipids and have provided insight into the underlying mechanisms of lipid homeostasis. Future research is needed to determine whether these loci may be novel targets for lipid-lowering therapy and for reducing cardiovascular disease risk. In addition, the proportion of genetic variance explained by these lipid loci is still limited and new large-scale genetic studies are ongoing to identify additional common and rare variants associated with lipid levels.

Unexpected roles for PCSK9 in lipid metabolism

To consider the evidence that PCSK9 has effects on lipoprotein metabolism that are in addition to its role in promoting the degradation of the LDL receptor. Transgenic mice expressing human PCSK9 under physiological control have recently been described. As well as the expected effects on LDL-receptor protein levels in the liver, mice expressing the gain-of-function mutant D374Y secrete more triglyceride than control mice or mice expressing wild-type PCSK9, supporting earlier suggestions that apoB synthesis is increased in hepatocytes expressing D374Y PCSK9 and that patients heterozygous for PCSK9 mutations have increased apoB synthesis. No increase in triglyceride secretion was observed in LDLR mice, suggesting that the effect of PCSK9 on triglyceride secretion is to some extent independent of the LDL receptor. Other recent studies have shown an association between serum PCSK9 concentration and serum triglyceride, but care has to be taken in interpretation of these results as it has also been shown that the level of PCSK9 in human serum shows strong diurnal variation. Understanding the physiology of PCSK9 is important because this protein has become a major new target for lipid lowering therapy.