scholarly journals PCSK9 gene participates in the development of primary dyslipidemias

2021 ◽  
Vol 24 (1) ◽  
pp. 5-14
Author(s):  
D Matías-Pérez ◽  
AD Pérez-Santiago ◽  
MA Sánchez Medina ◽  
JJ Alpuche Osorno ◽  
IA García-Montalvo
Keyword(s):  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atheromatous Plaque ◽  
Statin Intolerance ◽  
Blood Concentrations ◽  
Pcsk9 Gene ◽  
Atherosclerotic Plaque Formation

Abstract Dyslipidemias are a group of diseases, which are characterized by abnormal blood concentrations of cholesterol, triglycerides and/or low-density lipoprotein-cholesterol (LDL-c). Dyslipidemia is a determinant condition for the progress of an atherosclerotic plaque formation. The resulting atherogenicity is due to at least two mechanisms: first, to the accumulation in the plasma of lipid particles that have the capacity to alter the function of the endothelium and deposit at the atheromatous plaque, and second, at an insufficient concentration of multifactorial type of high density lipoprotein-cholesterol (HDL-c), whose function is to protect against the development of atherosclerosis. Its highest prevalence is encountered among individuals with diabetes, hypertension or overweight. Hyperlipidemia is one of the main predisposing factors for the development of cardiovascular disease. Hyperlipidemia can be the result of a genetic condition, the secondary expression of a primary process or the consequence of exogenous factors (food, cultural, socio-economic, etc.), all of which lead to the elevation of plasma lipid levels. The objective of this study was to carry out an analysis of the genes involved in the development of dyslipidemias that lead to cardiovascular disease with special emphasis on the proprotein convertase subtilin/kexin type 9 (PCSK9) gene. The PCSK9 gene participates in the development of primary dyslipidemias, mainly familial hypercholesterolemia, currently the pharmacological treatment of choice to reduce LDL-c are statins, however, it has been observed that these have been insufficient to eliminate cardiovascular risk, especially in subjects with primary forms of hypercholesterolemia related to genetic mutations, or statin intolerance.

scholarly journals Cardiovascular Disease in Women with Chronic Renal Failure

2015 ◽  
Vol 16 (1) ◽  
pp. 14-17
Author(s):  
Nwamaka Chiji Okenzere ◽  
Chukwubike Udoka Okeke
Keyword(s):  
Cardiovascular Disease ◽  
Renal Failure ◽  
Chronic Renal Failure ◽  
Low Density Lipoprotein ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Control Group ◽  
Dialysis Treatment ◽  
Female Patients

Objective: Patients with chronic renal failure have high burden of cardiovascular morbidity and mortality. This study was carried out to investigate the development of cardiovascular disease in chronic renal failure among female patients on dialysis treatment in Nigeria. Materials and Methods: A total of 40 adult female subjects participated in this study. 20 of them were apparently healthy and served as control group while the rest 20 were female patients with chronic renal failure (CRF) on dialysis treatment. Fasting blood samples were collected and their lipid profile, Total Cholesterol (TC), Triglyceride (TG), High Density Lipoprotein –Cholesterol (HDL-C), Low Density Lipoprotein –Cholesterol (LDL-C), and Very Low Density Lipoprotein –Cholesterol (VLDL-C) were estimated using enzymatic methods. The percentages of these parameters in circulation were obtained. The cardiovascular risk ratios (TC/HDL-C and LDL-C/HDL-C) were calculated. Result: The lipid profile of the chronic renal failure patients (TC 5.70±0.80mmol/l, TG 1.46±0.40mmol/l, LDL-C 3.50±0.2mmol/l, and VLDL-C 0.67±0.2mmol/l) were significantly higher (p<0.05) than that of control group (TC 4.03±0.13mmol/l, TG 1.10± 0.3mmol/l , LDL-C 1.85±0.5mmol/l, and VLDL-C 0.50± 0.01mmol/l) except HDL-C. HDL-C of the CRF patients (1.40±0.2mmol/l) was significantly lower (p<0.05) than that of healthy women (HDL-C 1.70± 0.04mmol/l). These depict no difference in the percentage of VLDL-C & TG in circulation between the control (VLDL –C 5% and TG 45%) and chronic renal failure patients (VLDL –C 5% and TG 44%). In CRF group, it was observed that 28% of the total plasma lipid (12.73mmol/l) was LDL-C but in healthy women, percentage of LDL-C in circulation (out of 9.18mmol/l) was 20%. It was also observed that 11% of the total plasma lipid (12.73mmol/l) in CRF patients was HDL-C but in healthy subjects, the percentage of HDL-C in circulation (out of 9.18mmol/l) was 19%. The cardiovascular risk indices (TC/HDL-C and LDL-C/HDL-C) of the CRF patients (TC/HDL-C 3.91±0.24 and LDL-C/HDL-C 2.50±0.01) were significantly higher (p<0.05) than those of the healthy subjects (TC/HDL-C 2.40±0.09, LDL-C/HDL-C 1.10±0.08). Conclusion: These results indicate that chronic renal failure is a risk factor to development of cardiovascular disease in female patients on dialysis.DOI: http://dx.doi.org/10.3329/jom.v16i1.22382 J MEDICINE 2015; 16 : 14-17

Eligibility for PCSK9 inhibitors based on the 2019 ESC/EAS and 2018 ACC/AHA guidelines

2020 ◽  
pp. 204748732094010
Author(s):  
Konstantinos C Koskinas ◽  
Baris Gencer ◽  
David Nanchen ◽  
Mattia Branca ◽  
David Carballo ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Coronary Syndrome ◽  
Coronary Syndromes

Aims The 2018 American College of Cardiology (ACC)/American Heart Association (AHA) and 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) lipid guidelines recently updated their recommendations regarding proprotein convertase subtilisin/kexin-9 inhibitors (PCSK9i). We assessed the potential eligibility for PCSK9i according to the new guidelines in patients with acute coronary syndromes. Methods and results We analysed a contemporary, prospective Swiss cohort of patients hospitalised for acute coronary syndromes. We modelled a statin intensification effect and an incremental ezetimibe effect on low-density lipoprotein-cholesterol levels among patients who were not on high-intensity statins or ezetimibe. One year after the index acute coronary syndrome event, treatment eligibility for PCSK9i was defined as low-density lipoprotein-cholesterol of 1.4 mmol/l or greater according to ESC/EAS guidelines. For ACC/AHA guidelines, treatment eligibility was defined as low-density lipoprotein-cholesterol of 1.8 mmol/l or greater in the presence of very high-risk atherosclerotic cardiovascular disease, defined by multiple major atherosclerotic cardiovascular disease events and/or high-risk conditions. Of 2521 patients, 93.2% were treated with statins (53% high-intensity statins) and 7.3% with ezetimibe at 1 year, and 54.9% had very high-risk atherosclerotic cardiovascular disease. Low-density lipoprotein-cholesterol levels less than 1.8 mmol/l and less than 1.4 mmol/l at 1 year were observed in 37.5% and 15.7% of patients, respectively. After modelling the statin intensification and ezetimibe effects, these numbers increased to 76.1% and 49%, respectively. The proportion of patients eligible for PCSK9i was 51% according to ESC/EAS criteria versus 14% according to ACC/AHA criteria. Conclusions In this analysis, the 2019 ESC/EAS guidelines rendered half of all post-acute coronary syndrome patients potentially eligible for PCSK9i treatment, as compared to a three-fold lower eligibility rate based on the 2018 ACC/AHA guidelines.

Abstract P43: Frequency and Predictors of Low-Density Lipoprotein Cholesterol Control and Appropriate Response to Elevated LDL-C Levels in Patients with Cardiovascular Disease

2011 ◽  
Vol 4 (suppl_2) ◽  
Author(s):  
Salim S Virani ◽  
Lechauncy D Woodard ◽  
Supicha Sookanan ◽  
Cassie R Landrum ◽  
Tracy H Urech ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Medication Possession Ratio ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
To Receive

Background: Although current cholesterol performance measures define good quality as low density lipoprotein cholesterol (LDL-C) levels < 100mg/dl in cardiovascular disease (CVD) patients, they provide a snap shot at one time point and do not inform whether an appropriate action was taken to manage elevated LDL-C levels. We assessed frequency and predictors of this appropriate response (AR). Methods: We used administrative data to assess 22,902 CVD patients receiving care in a Veterans Affairs network of 7 hospitals and affiliated clinics. We determined the proportion of CVD patients at LDL-C goal <100 mg/dl, and the proportion of patients with uncontrolled LDL-C levels (>100 mg/dl) who had an AR [defined as the initiation or dosage increase of a lipid lowering medication (LLM), addition of a new LLM, receipt of maximum dosage or >1 LLM, or LDL-C reading <100 mg/dl] at 45 days follow-up. Logistic regression was performed to evaluate facility, provider and patient characteristics associated with AR. Results: LDL-C levels were at goal in 16,350 (71.4%) patients. An additional 2,110 (9.2%) had an AR at 45 days of follow-up. Controlling for clustering between facilities and patient's illness severity, history of diabetes (OR 1.18, 95% CI 1.03-1.35), hypertension (OR 1.21, 95% CI 1.02-1.44), patients showing good medication adherence (medication possession ratio > 0.8) [OR 2.29, 95% CI 1.99-2.64] were associated with AR. Older CVD patients (age >75 years) were less likely to receive AR (OR 0.60, 95% CI 0.52-0.70). Teaching vs. non-teaching facility (p=0.40), physician vs. non-physician provider (p=0.14), specialist vs. non-specialist primary care provider (p=0.12), and patient's race (p=0.12) were not predictors of AR. Conclusion: Among patients with CVD and LDL-C above guideline recommended levels, only one-third receive AR. Diabetic and hypertensive CVD patients are more likely to receive AR, whereas older Veterans with CVD receive AR less often likely reflecting providers' belief of lack of efficacy from treatment intensification in older CVD patients. Our findings are important for quality improvement and policy making initiatives as they provide more actionable information compared with isolated LDL-C goal attainment as a quality indicator.

Abstract P181: Atherogenic Lipoproteins and Incident Atherosclerotic Cardiovascular Disease in the Framingham Offspring Study

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Hiroaki Ikezaki ◽  
Elise Lim ◽  
Ching-Ti Liu ◽  
L Adrienne Cupples ◽  
Bela F Asztalos ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Significant Information ◽  
Ascvd Risk

Introduction: Elevated plasma low-density lipoprotein cholesterol (LDL-C), small-dense LDL-C (sdLDL-C), LDL-triglyceride (LDL-TG), triglycerides (TG), remnant-lipoprotein cholesterol (RLP-C), triglyceride-rich lipoprotein-C (TRL-C), very low-density lipoprotein cholesterol (VLDL-C), and lipoprotein(a) [Lp(a)] levels have been associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. However, these parameters have not been included in risk factors for ASCVD in the pooled cohort equation (PCE). Hypothesis: We assessed the hypothesis that these atherogenic lipoprotein parameters add significant information for ASCVD risk prediction in the Framingham Offspring Study. Methods: We evaluated 3,147 subjects without ASCVD at baseline (mean age 58 years) from participants of Framingham Offspring Study cycle 6, 677 (21.5%) of whom developed inclusive ASCVD over 16 years. Biomarkers of risk were assessed in frozen plasma samples. Total cholesterol, TG, HDL-C, direct LDL-C, sdLDL-C, LDL-TG, Lp(a), RLP-C, and TRL-C were measured by standardized automated analysis. Calculated LDL-C, large buoyant low-density lipoprotein cholesterol (lbLDL-C), VLDL-C, and non-HDL-C values were calculated. Data were analyzed using Cox proportional regression analysis and net reclassification improvement (NRI) analysis to identify parameters significantly associated with the incidence of ASCVD after controlling for standard ASCVD risk factor and applying the PCE model. Results: All specialized lipoprotein parameters were significant ASCVD risk factors on univariate analysis, but only direct LDL-C, sdLDL-C, and Lp(a) were significant on multivariate analysis with standard risk factors in the model. Together these parameters significantly improved the model c statistic (0.716 vs 0.732, P < 0.05) and net risk reclassification (mean NRI 0.104, P < 0.01) for ASCVD risk. Using the ASCVD risk pooled cohort equation, sdLDL-C, TG, LDL-TG, LDL-C, RLP-C, and TRL-C individually added significant information, but no other parameter added significant information with sdLDL-C (hazard ratio 1.30 for 75th vs 25th percentile, P < 0.0001) in the model. Conclusions: In multivariate analysis, sdLDL-C, direct LDL-C, and Lp(a) contributed significantly to ASCVD risk, but only sdLDL-C added significant risk information to the PCE model, indicating that sdLDL-C may be the most atherogenic lipoprotein particle.

scholarly journals Alirocumab therapy in individuals with type 2 diabetes mellitus and atherosclerotic cardiovascular disease: analysis of the ODYSSEY DM-DYSLIPIDEMIA and DM-INSULIN studies

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Kausik K. Ray ◽  
Stefano Del Prato ◽  
Dirk Müller-Wieland ◽  
Bertrand Cariou ◽  
Helen M. Colhoun ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Open Label ◽  
Double Blind ◽  
Mixed Dyslipidemia

Abstract Background Individuals with diabetes often have high levels of atherogenic lipoproteins and cholesterol reflected by elevated low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and LDL particle number (LDL-PN). The presence of atherosclerotic cardiovascular disease (ASCVD) increases the risk of future cardiovascular events. We evaluated the efficacy and safety of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, alirocumab, among individuals with type 2 diabetes (T2DM), high LDL-C or non-HDL-C, and established ASCVD receiving maximally tolerated statin in ODYSSEY DM-DYSLIPIDEMIA (NCT02642159) and DM-INSULIN (NCT02585778). Methods In DM-DYSLIPIDEMIA, individuals with T2DM and mixed dyslipidemia (non-HDL-C ≥ 100 mg/dL; n = 413) were randomized to open-label alirocumab 75 mg every 2 weeks (Q2W) or usual care (UC) for 24 weeks, with UC options selected before stratified randomization. In DM-INSULIN, insulin-treated individuals with T2DM (LDL-C ≥ 70 mg/dL; n = 441) were randomized in a double-blind fashion to alirocumab 75 mg Q2W or placebo for 24 weeks. Study participants also had a glycated hemoglobin < 9% (DM-DYSLIPIDEMIA) or < 10% (DM-INSULIN). Alirocumab dose was increased to 150 mg Q2W at week 12 if week 8 LDL-C was ≥ 70 mg/dL (DM-INSULIN) or non-HDL-C was ≥ 100 mg/dL (DM-DYSLIPIDEMIA). Lipid reductions and safety were assessed in patients with ASCVD from these studies. Results This analysis included 142 DM-DYSLIPIDEMIA and 177 DM-INSULIN participants with ASCVD, including 95.1% and 86.4% with coronary heart disease, and 32.4% and 49.7% with microvascular diabetes complications, respectively. At week 24, alirocumab significantly reduced LDL-C, non-HDL-C, ApoB, and LDL-PN from baseline versus control. This translated into a greater proportion of individuals achieving non-HDL-C < 100 mg/dL (64.6% alirocumab/23.8% UC [DM-DYSLIPIDEMIA]; 65.4% alirocumab/14.9% placebo [DM-INSULIN]) and ApoB < 80 mg/dL (75.1% alirocumab/35.4% UC and 76.8% alirocumab/24.8% placebo, respectively) versus control at week 24 (all P < 0.0001). In pooling these studies, 66.4% (alirocumab) and 67.0% (control) of individuals reported treatment-emergent adverse events. The adverse event pattern was similar with alirocumab versus controls. Conclusions Among individuals with T2DM and ASCVD who had high non-HDL-C/LDL-C levels despite maximally tolerated statin, alirocumab significantly reduced atherogenic cholesterol and LDL-PN versus control. Alirocumab was generally well tolerated. Trial registration Clinicaltrials.gov. NCT02642159. Registered 30 December 2015 and Clinicaltrials.gov. NCT02585778. Registered 23 October 2015

CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE MANAGEMENT OF DYSLIPIDEMIA AND PREVENTION OF CARDIOVASCULAR DISEASE ALGORITHM – 2020 EXECUTIVE SUMMARY

2020 ◽  
Vol 26 (10) ◽  
pp. 1196-1224 ◽  
Author(s):  
Yehuda Handelsman ◽  
Paul S. Jellinger ◽  
Chris K. Guerin ◽  
Zachary T. Bloomgarden ◽  
Eliot A. Brinton ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Icosapent Ethyl ◽  
Lipid Disorders ◽  
Ascvd Risk

The treatment of lipid disorders begins with lifestyle therapy to improve nutrition, physical activity, weight, and other factors that affect lipids. Secondary causes of lipid disorders should be addressed, and pharmacologic therapy initiated based on a patient’s risk for atherosclerotic cardiovascular disease (ASCVD). Patients at extreme ASCVD risk should be treated with high-intensity statin therapy to achieve a goal low-density lipoprotein cholesterol (LDL-C) of <55 mg/dL, and those at very high ASCVD risk should be treated to achieve LDL-C <70 mg/dL. Treatment for moderate and high ASCVD risk patients may begin with a moderate-intensity statin to achieve an LDL-C <100 mg/dL, while the LDL-C goal is <130 mg/dL for those at low risk. In all cases, treatment should be intensified, including the addition of other LDL-C-lowering agents (i.e., proprotein convertase subtilisin/kexin type 9 inhibitors, ezetimibe, colesevelam, or bempedoic acid) as needed to achieve treatment goals. When targeting triglyceride levels, the desirable goal is <150 mg/dL. Statin therapy should be combined with a fibrate, prescription-grade omega-3 fatty acid, and/or niacin to reduce triglycerides in all patients with triglycerides ≥500 mg/dL, and icosapent ethyl should be added to a statin in any patient with established ASCVD or diabetes with ≥2 ASCVD risk factors and triglycerides between 135 and 499 mg/dL to prevent ASCVD events. Management of additional risk factors such as elevated lipoprotein(a) and statin intolerance is also described. Abbreviations: AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; ACS = acute coronary syndrome; apo B = apolipoprotein B; ASCVD = atherosclerotic cardiovascular disease; BA = bempedoic acid; CAC = coronary artery calcium; CHD = coronary heart disease; CK = creatine kinase; CKD = chronic kidney disease; DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; FCS = familial chylomicronemia syndrome; FDA = United States Food and Drug Administration; FOURIER = Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk; HDL-C = high-density lipoprotein cholesterol; HeFH = heterozygous familial hypercholesterolemia; HoFH = homozygous familial hyper-cholesterolemia; hsCRP = high-sensitivity C reactive protein; IDL = intermediate-density lipoproteins; IMPROVE-IT = Improved Reduction of Outcomes: Vytorin Efficacy International Trial; IPE = icosapent ethyl; LDL-C = low-density lipoprotein cholesterol; Lp(a) = lipoprotein a; MACE = major adverse cardiovascular events; MI = myocardial infarction; OSA = obstructive sleep apnea; PCSK9 = proprotein convertase subtilisin/kexin type 9; REDUCE-IT = Reduction of Cardiovascular Events with EPA-Intervention Trial; UKPDS = United Kingdom Prospective Diabetes Study; U.S. = United States; VLDL = very-low-density lipoproteins

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