scholarly journals 6th Hellenic Congress in Athens, of the Hellenic Atherosclerosis Society, on the 04-06 December 2014 Novel Pharmacologic Treatments of Familial Hypercholesterolaemia

2015 ◽  
Vol 9 (1) ◽  
pp. 73-77
Author(s):  
Athyros VG
Keyword(s):  
Familial Hypercholesterolaemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Automatic Device ◽  
Loss Of Function ◽  
Ldl Apheresis ◽  
Cvd Risk ◽  
Atherosclerosis Risk In Communities ◽  
Lipid Disorder ◽  
Pharmacologic Treatments

Familial hypercholesterolaemia (FH) is the most common inherited monogenic lipid disorder. It is caused by mutations of genes related to low density lipoprotein (LDL) receptors, apolipoprotein B or proprotein convertase subtilisin/kexin type 9 (PCSK9). Homozygous FH (HoFH; 1/400,000 births) is treated by LDL apheresis. Recently lomitapide has been used for the treatment of HoFH as a monotherapy or in addition to LDL apheresis. Heterozygous FH (HeFH), 1/250-1/200 births, is associated with an increased cardiovascular disease (CVD) risk. The main treatment for HeFH has been high doses of high intensity statins plus ezetimibe. However, this is not usually enough to attain LDL-C targets, especially in those with overt CVD or equivalents (LDL-C goal of<70 mg/dl). Data from the Atherosclerosis Risk in Communities study showed that loss of function mutations of PCSK9 were associated with a 28% lower LDL-C level and an 88% reduction in the risk of CVD in blacks, while in whites these numbers were 15% and 47%, respectively. This led to the development of technology to block PCSK9 with monoclonal human antibodies (e.g. evolocumab and alirocumab). These antibodies have been shown in phase II and III trials to be safe and to produce reductions in LDL-C levels by around 60% either as monotherapy or on top of optimal therapy with statins and ezetimibe. These antibodies are administered subcutaneously every 2 weeks with an automatic device. Anti-PCSK9 antibodies are expected to be licensed soon (? in 2015) and are considered by many as “the statins of the 21st century”.

Should we Consider Lipoprotein (a) in Cardiovascular Disease Risk Assessment in Patients with Familial Hypercholesterolaemia?

2019 ◽  
Vol 24 (31) ◽  
pp. 3665-3671 ◽  
Author(s):  
Panagiotis Anagnostis ◽  
Pavlos Siolos ◽  
Dimitrios Krikidis ◽  
Dimitrios G. Goulis ◽  
John C. Stevenson
Keyword(s):  
Cardiovascular Disease ◽  
Familial Hypercholesterolaemia ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Pcsk9 Inhibitors ◽  
Cvd Risk ◽  
Lipoprotein A ◽  
Increased Risk

Background: Familial hypercholesterolaemia (FH) is a genetically determined lipid disorder, affecting 1 per 200-500 individuals in the general population. It is significantly and independently associated with an increased risk of Cardiovascular Disease (CVD), although it remains still an underrecognized and undertreated disease. Lipoprotein (a) [Lp(a)] is a low-density-lipoprotein (LDL)-like molecule, containing an additional protein, apolipoprotein (a). Objective: This review aims to present and discuss available data on the role of Lp(a) in patients with FH, in terms of its potential augmentation of CVD risk. Methods: A comprehensive search of the literature was performed to identify studies evaluating the CV effects of Lp(a) in patients with FH. Results: Lp(a) has been recognised as an independent risk factor for CVD, mainly coronary artery disease (CAD). Most, but not all, studies show increased Lp(a) concentrations in adults and children with FH. There is also evidence of an independent association between Lp(a) and CVD (mainly CAD) risk in these patients. Conclusion: Some therapeutic modalities, such as niacin, oestrogens, tibolone and proprotein convertase subtilisin/ kexin type 9 (PCSK9) inhibitors may effectively reduce Lp(a) concentrations by 25-30%, although their clinical benefit of this effect remains to be established.

Lipids

2015 ◽  
Author(s):  
Željko Reiner ◽  
Olov Wiklund ◽  
John Betteridge
Keyword(s):  
Familial Hypercholesterolaemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Lifestyle Changes ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
First Line ◽  
Cvd Risk ◽  
Low Concentrations

Dyslipidaemia, particularly elevated low-density lipoprotein (LDL) cholesterol, is one of the most important risk factors for cardiovascular disease (CVD). Low concentrations of high-density lipoprotein (HDL) cholesterol are independently associated with high CVD risk, while moderately elevated triglycerides are considered to be a marker of increased CVD risk. The presence of dyslipidaemias secondary to other conditions must be excluded before beginning treatment. All patients with familial hypercholesterolaemia are at high risk and should be treated by lipid-lowering therapy. Lifestyle changes are the backbone of treatment for dyslipidaemia. Statins are recommended as the first-line drugs for hypercholesterolaemia while fibrates are used primarily to decrease elevated triglycerides. If the treatment targets cannot be reached by monotherapy with lipid-lowering drugs, combination treatment may be needed.

PCSK9 Inhibitors: Novel Therapeutic Strategies for Lowering LDLCholesterol

2018 ◽  
Vol 19 (2) ◽  
pp. 165-176 ◽  
Author(s):  
Yan Wang ◽  
Zhao-Peng Liu
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Maximum Tolerated Dose ◽  
Therapeutic Strategies ◽  
Low Density ◽  
Pcsk9 Inhibitors ◽  
Cvd Risk ◽  
Safety Issues ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Statins are currently the major therapeutic strategies to lower low-density lipoprotein cholesterol (LDL-C) levels. However, a number of hypercholesterolemia patients still have a residual cardiovascular disease (CVD) risk despite taking the maximum-tolerated dose of statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low-density lipoprotein receptor (LDLR), inducing its degradation in the lysosome and inhibiting LDLR recirculating to the cell membranes. The gain-offunction mutations in PCSK9 elevate the LDL-C levels in plasma. Therefore, PCSK9 inhibitors become novel therapeutic approaches in the treatment of hypercholesterolemia. Several PCSK9 inhibitors have been under investigation, and much progress has been made in clinical trials, especially for monoclonal antibodies (MoAbs). Two MoAbs, evolocumab and alirocumab, are now in clinical use. In this review, we summarize the development of PCSK9 inhibitors, including antisense oligonucleotides (ASOs), small interfering RNA (siRNA), small molecule inhibitor, MoAbs, mimetic peptides and adnectins, and the related safety issues.

scholarly journals Reduction of Vascular Inflammation, LDL-C, or Both for the Protection from Cardiovascular Events?

2018 ◽  
Vol 12 (1) ◽  
pp. 29-40 ◽  
Author(s):  
Andromachi Reklou ◽  
Michael Doumas ◽  
Konstantinos Imprialos ◽  
Konstantinos Stavropoulos ◽  
Dimitris Patoulias ◽  
...  
Keyword(s):  
Vascular Inflammation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Myocardial Damage ◽  
Lipid Lowering ◽  
Human Antibody ◽  
Low Grade ◽  
Cvd Risk ◽  
Expensive Drug ◽  
Arterial Inflammation

Background: Low density lipoprotein cholesterol (LDL-C) and low grade arterial inflammation are key pathogenic factors for atherosclerosis and its manifestation, cardiovascular disease (CVD). Objective: In this narrative review we assessed if decreasing LDL-C levels or inflammation or both is more effective in reducing CVD events. Results: In the Scandinavian Simvastatin Survival Study (4S), all statin trials of the 90s’ and the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) the benefit came from the LDL-C reduction. In the GREak and Atorvastatin Coronary heart disease Evaluation (GREACE), the Treating to New Targets (TNT), and the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trials both mechanisms in combination produced significant benefits. In the Atorvastatin for Reduction of MYocardial Damage during Angioplasty (ARMYDA) trials and the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) with a human antibody targeting IL-1β with no lipid lowering effect, the reduction in arterial inflammation played the only beneficial role because there was no change in lipids levels. Conclusion: Both LDL-C and inflammation reduction are beneficial to the reduction of CVD risk. However, canakinumab is a very expensive drug that only induced a 15% reduction in CVD events, thus drastically reducing the possibility for it to be used in clinical practice. Besides, canakinumab is associated with increased infections, some fatal. A potent statin with anti-inflammatory effects is probably the best choice for the majority of those needing hypolipidaemic drug therapy.

Identifying the prevalence of undiagnosed cardiovascular disease risk factors in healthy Indians

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
S Thanvi ◽  
P Thakkar
Keyword(s):  
Risk Factors ◽  
Heart Attack ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Healthy Individuals ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Health Checkup ◽  
Study Population ◽  
High Level

Abstract Funding Acknowledgements Type of funding sources: None. Introduction   Cardiovascular disease (CVD) including heart disease and stroke, is the leading cause of death globally and in India.  The importance of primary prevention, defined as interventions designed to modify adverse risk factors with the goal of preventing an initial CVD event has been established beyond doubt by several population based studies in healthy individuals. While there have been many studies defining the high prevalence in CVD risk factors in Indian population, this study sought to determine the prevalence of undiagnosed modifiable CVD risk factors in healthy individuals.  Methods The  cross sectional, analytical study was carried out at the hospitals, from 1st April 2015 to 31st dec 2017. Subjects between 18 - 70 years of age who were healthy and were undergoing health checkup were included in the study. A total of 5000 patients were screened, those having existing CVD risk factors were excluded from the study.  This study was approved by the institutional ethics committee of the hospital. Written informed consent was obtained from all subjects. The data collection record sheet was prepared based on validated and standardized questionnaires which was used to enter all data.  Physical examination for vitals and BMI was done by qualified physicians. Blood investigations were done for diabetes and dyslipidemia and thyroid dysfunction. ACC/AHA criteria was used for diagnosis of  hypertension, ADA criteria for diabetes. Joint British society 3 risk score and ASCVD risk score was calculated using standard calculators. Results At screening, 4998 participants aged ≥18 years were approached to participate in study. The study population included 2705 men (68.1%) and 1265 women (31.9%) with a mean age of 68± 18.8 years. The most prevalent risk factor was overweight and obesity (71.2%). The prevalence of undiagnosed HTN was 73.3%, undiagnosed pre-diabetes was 24.9% and undiagnosed diabetes was 28.3%. Out of total, 44.3% subjects had high level of low-density lipoprotein and 36.6% subjects had low level of high-density lipoprotein, 20.1% subjects had high level of very-low density lipoprotein (VLDL) and 17.3% subjects had high level of triglyceride. Tobacco smoking was present in 7.7% of the population. The risk estimation predicted 29.1% of the study participants to have more than 10% risk of heart attack/stroke risk at 10 years. Conclusion Our study reveals a fairly good snapshot of CVDs risk factors in healthy general population. Increased prevalence of high BMI, undiagnosed HTN, diabetes, dyslipidemia was present in our study population.  The population had significantly high predicted risk of heart attack/stroke. These findings warrant the need of community based life style modifications, regular health checkup for healthy population for early detection and modification of CVD risk factors.

scholarly journals Mitochondrial Lipid Homeostasis at the Crossroads of Liver and Heart Diseases

2021 ◽  
Vol 22 (13) ◽  
pp. 6949
Author(s):  
Siarhei A. Dabravolski ◽  
Evgeny E. Bezsonov ◽  
Mirza S. Baig ◽  
Tatyana V. Popkova ◽  
Alexander N. Orekhov
Keyword(s):  
Heart Diseases ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Liver Mitochondria ◽  
Atherogenic Dyslipidemia ◽  
Cvd Risk ◽  
Alcoholic Fatty Liver ◽  
Cholesterol Levels ◽  
Mitochondrial Lipid ◽  
Cardioprotective Effects

The prevalence of NAFLD (non-alcoholic fatty liver disease) is a rapidly increasing problem, affecting a huge population around the globe. However, CVDs (cardiovascular diseases) are the most common cause of mortality in NAFLD patients. Atherogenic dyslipidemia, characterized by plasma hypertriglyceridemia, increased small dense LDL (low-density lipoprotein) particles, and decreased HDL-C (high-density lipoprotein cholesterol) levels, is often observed in NAFLD patients. In this review, we summarize recent genetic evidence, proving the diverse nature of metabolic pathways involved in NAFLD pathogenesis. Analysis of available genetic data suggests that the altered operation of fatty-acid β-oxidation in liver mitochondria is the key process, connecting NAFLD-mediated dyslipidemia and elevated CVD risk. In addition, we discuss several NAFLD-associated genes with documented anti-atherosclerotic or cardioprotective effects, and current pharmaceutical strategies focused on both NAFLD treatment and reduction of CVD risk.

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