scholarly journals Lipoprotein(a) Where Do We Stand? From the Physiopathology to Innovative Terapy

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 838
Author(s):  
Gabriella Iannuzzo ◽  
Maria Tripaldella ◽  
Vania Mallardo ◽  
Mena Morgillo ◽  
Nicoletta Vitelli ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Treatment Options ◽  
Strong Association ◽  
Elevated Serum ◽  
Serum Levels ◽  
Epidemiologic Studies ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lipoprotein A ◽  
Premature Cardiovascular Disease

A number of epidemiologic studies have demonstrated a strong association between increasing lipoprotein a [Lp(a)] and cardiovascular disease. This correlation was demonstrated independent of other known cardiovascular (CV) risk factors. Screening for Lp(a) in the general population is not recommended, although Lp(a) levels are predominantly genetically determined so a single assessment is needed to identify patients at risk. In 2019 ESC/EAS guidelines recommend Lp(a) measurement at least once a lifetime, fo subjects at very high and high CV risk and those with a family history of premature cardiovascular disease, to reclassify patients with borderline risk. As concerning medications, statins play a key role in lipid lowering therapy, but present poor efficacy on Lp(a) levels. Actually, treatment options for elevated serum levels of Lp(a) are very limited. Apheresis is the most effective and well tolerated treatment in patients with high levels of Lp(a). However, promising new therapies, in particular antisense oligonucleotides have showed to be able to significantly reduce Lp(a) in phase II RCT. This review provides an overview of the biology and epidemiology of Lp(a), with a view to future therapies.

scholarly journals Lipoprotein Apheresis in Patients With Maximally Tolerated Lipid-Lowering Therapy, Lipoprotein(a)-Hyperlipoproteinemia, and Progressive Cardiovascular Disease

Circulation ◽  
2013 ◽  
Vol 128 (24) ◽  
pp. 2567-2576 ◽  
Author(s):  
Josef Leebmann ◽  
Eberhard Roeseler ◽  
Ulrich Julius ◽  
Franz Heigl ◽  
Ralf Spitthoever ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lipoprotein A ◽  
Lipoprotein Apheresis ◽  
Lowering Therapy

scholarly journals AB0875-HPR NON-PHARMACOLOGICAL AND PHARMACOLOGICAL APPROACHES TO THE MANAGEMENT OF PATIENTS WITH OSTEOARTHRITIS AND LIPID METABOLISM DISORDERS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1461.1-1461
Author(s):  
T. Rogatkina ◽  
O. Korolik ◽  
V. Polyakov ◽  
G. Kravtsov ◽  
Y. Polyakova
Keyword(s):  
Physical Activity ◽  
Cardiovascular Disease ◽  
Lipid Metabolism ◽  
Lipid Profile ◽  
Fat Mass ◽  
Prognostic Significance ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lipid Metabolism Disorders ◽  
Group I

Background:Attention is drawn to the frequent combination of osteoarthritis (OA) with cardiovascular disease. Non-specific inflammation plays a significant role in the pathogenesis of OA and atherosclerosis. Limiting the physical activity of patients with OA is an additional important factor aggravating the course of cardiovascular disease (CVD). Chronic pain syndrome, causing a neuroendocrine response, is often the cause of the development of complications of atherosclerotic disease. Dyslipidemia is the main cause of atherosclerosis and vascular thrombosis.Objectives:To study variants of lipid metabolism disorders in female and male patients of different age groups with osteoarthritis.Methods:Case histories of 90 patients with OA were analyzed. The average age of patients was 63.27 ± 11.31 years. The average body mass index (BMI) is 39.8 ± 3.2. All patients underwent questionnaires, general clinical and biochemical blood tests with lipid profile determination, anthropometry, bioimpedansometry, and the main metabolic rate assessment using indirect calorimetry in dynamics (at the beginning of the study and after 3 months).Results:Burdened heredity for obesity, arterial hypertension (AH), diabetes mellitus (DM) was revealed. AH was diagnosed in 76 patients (84.4%), type II diabetes in 17 (18.9%), dyslipidemia and hypercholesterolemia in 56 (62.2%). Statins were taken by 43 patients (47.8%) - group I patients, which is associated with low adherence to therapy, group II included patients who did not initially take statins or stopped taking them at least 6 months before inclusion in the study.Against the background of diet therapy and physiotherapy exercises, BMI (R0.99; p <0.05), fat mass (R0.95; p <0.05) significantly decreased, lipid profile normalization was noted: total cholesterol (R0.66; p <0 .05), LDL (R0.69; p <0.05), HDL (R0.95; p <0.05), TG (R0.57; p <0.05), AST decreased (R0.64; p <0.05) and ALT (R0.76; p <0.05) in both groups of patients, regardless of lipid-lowering therapy. A decrease in fat mass correlated with TG levels (R0.51; p <0.05), an increase in skeletal muscle mass (R0.60; p <0.05), lean mass (R0.72; p <0.05), and active cell mass (R0.59; p <0.05). The lipid profile in the I group of patients was significantly better before and at the end of the study. Long-term effects have not been investigated due to the short duration of the study.Conclusion:In patients with OA, a high frequency of concomitant diseases of the cardiovascular system, lipid metabolism disorders was found. Non-drug therapy has a positive effect on the lipid profile and the level of transaminases. The decrease in body weight due to loss of fat mass reliably correlates with the level of TG. Timely use of statins contributes to the normalization of the lipid profile, reduces the risk of cardiovascular disease in patients with OA. It is necessary to study lipid profile disorders in patients with OA with recommendations for lifestyle modification (diet, physical activity), and if necessary, prescribe lipid-correcting therapy.References:[1]E. Simakova, B. Zavodovsky, L. Sivordova [et al]. Prognostic significance of lipid disorders markers determination in pathogenesis of osteoarthritis. Vestnik Rossijskoj voenno-medicinskoj akademii. 2013. No. 2 (42). P.29-32.[2]Zavodovsky B.V., Sivordova L.E. Prognostic significance value of definition of leptin level determination in osteoarthritis. Siberian Medical Journal (Irkutsk). 2012; 115(8):069-072.Disclosure of Interests:None declared

scholarly journals Lipoprotein(a) and Cardiovascular Outcomes after Revascularization of Carotid and Lower Limbs Arteries

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 257
Author(s):  
Marat V. Ezhov ◽  
Narek A. Tmoyan ◽  
Olga I. Afanasieva ◽  
Marina I. Afanasieva ◽  
Sergei N. Pokrovsky
Keyword(s):  
Primary Endpoint ◽  
Cardiovascular Events ◽  
Cardiovascular Outcomes ◽  
Lower Limbs ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Cox Regression Analysis ◽  
Lipoprotein A ◽  
Secondary Endpoints

Background: Despite high-intensity lipid-lowering therapy, there is a residual risk of cardiovascular events that could be associated with lipoprotein(a) (Lp(a)). It has been shown that there is an association between elevated Lp(a) level and cardiovascular outcomes in patients with coronary heart disease. Data about the role of Lp(a) in the development of cardiovascular events after peripheral revascularization are scarce. Purpose: To evaluate the relationship of Lp(a) level with cardiovascular outcomes after revascularization of carotid and lower limbs arteries. Methods: The study included 258 patients (209 men, mean age 67 years) with severe carotid and/or lower extremity artery disease, who underwent successful elective peripheral revascularization. The primary endpoint was the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. The secondary endpoint was the composite of primary endpoint and repeated revascularization. Results: For 36-month follow-up, 29 (11%) primary and 128 (50%) secondary endpoints were registered. There was a greater risk of primary (21 (8%) vs. 8 (3%); hazard ratio (HR), 3.0; 95% confidence interval (CI) 1.5–6.3; p < 0.01) and secondary endpoints (83 (32%) vs. 45 (17%), HR, 2.8; 95% CI 2.0–4.0; p < 0.01) in patients with elevated Lp(a) level (≥30 mg/dL) compared to patients with Lp(a) < 30 mg/dL. Multivariable-adjusted Cox regression analysis revealed that Lp(a) was independently associated with the incidence of cardiovascular outcomes. Conclusions: Patients with peripheral artery diseases have a high risk of cardiovascular events. Lp(a) level above 30 mg/dL is significantly and independently associated with cardiovascular events during 3-year follow-up after revascularization of carotid and lower limbs arteries.

scholarly journals D-thyroxine reduces lipoprotein(a) serum concentration in dialysis patients.

1998 ◽  
Vol 9 (1) ◽  
pp. 90-96
Author(s):  
C Bommer ◽  
E Werle ◽  
I Walter-Sack ◽  
C Keller ◽  
F Gehlen ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Ldl Cholesterol ◽  
Clinical Symptoms ◽  
Hormone Secretion ◽  
Elevated Serum ◽  
Serum Levels ◽  
Controlled Study ◽  
Dialysis Patients ◽  
Lipoprotein A ◽  
Thyroxine Therapy

Uremia raises lipoprotein(a) (Lp(a)) serum concentration and the risk of arteriosclerosis in dialysis patients. The treatment of high Lp(a) levels is not satisfactory today. The decrease of Lp(a) in hypothyroid patients on L-T4 therapy raised the question of whether dextro-thyroxine (D-thyroxine) reduces not only serum cholesterol, but also Lp(a) serum concentration. In a single-blind placebo-controlled study, the influence of D-thyroxine therapy on Lp(a) serum concentration was evaluated in 30 hemodialysis patients with elevated Lp(a) serum levels. Lp(a) was quantified in parallel by two methods, i.e., rocket immunoelectrophoresis and nephelometry, and apo(a) isoforms were determined by a sensitive immunoblotting technique. Regardless of the apo(a) isoforms, 6 mg/d D-thyroxine reduced elevated Lp(a) levels significantly by 27 +/- 13% in 20 dialysis patients (P < 0.001) compared with 10 control subjects (-9.9 +/- 8.4%). In parallel, D-thyroxine therapy significantly lowered total cholesterol (P < 0.001), LDL cholesterol (P < 0.001), and LDL cholesterol/HDL cholesterol ratio (P < 0.01); raised T4 and T3 serum levels; and suppressed thyroid-stimulating hormone secretion without causing clinical symptoms of hyperthyroidism in any of the patients. D-Thyroxine reduces elevated serum Lp(a) concentration in dialysis patients. The effect in nondialysis patients can be expected but remains to be proven.

P647An audit of possible familial hypercholesterolaemia in general practice

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J Gallagher ◽  
M McGuckin ◽  
D Behan ◽  
P Harrington
Keyword(s):  
Cardiovascular Disease ◽  
General Practice ◽  
Familial Hypercholesterolaemia ◽  
Lipid Lowering ◽  
Inclusion Criteria ◽  
Clinical Notes ◽  
Structured Care ◽  
Premature Cardiovascular Disease ◽  
History Of ◽  
The Mean

Abstract Background Familial hypercholesterolaemia (FH) is an autosomal dominant condition associated with elevated total cholesterol and low-density lipoprotein (LDL). It confers an increased risk of premature cardiovascular disease and associated mortality. It is estimated that the majority of patients with FH in Ireland are undiagnosed and structured care programmes are not available. Purpose To undertake an audit of those patients in a general practice with possible FH Methods A retrospective audit was carried out on the patients attending a GP practice. Inclusion criteria for the study were as follows: LDL level >4.9mmol/L Triglyceride level (<2mmol/L) Data was collected from the patients' clinical notes and patients were interviewed to acquire additional details not available in the clinical notes where possible. A Dutch Lipid Clinic Network Score (DLCNS) was calculated for each patient. Results Of 5,438 patients with a LDL recorded 284 patients fulfilled the inclusion criteria. 52.4% were female. Mean age 60 years old (range: 19–95 years). The highest LDL level recorded for these patients ranged from 5.0 - 8.6 mmol/L, with a mean value of 5.4 mmol/L. The mean most recent LDL level was 3.6mmol/L (range: 1.0–6.3 mmol/L). 42 patients (14.8%) had a family history of premature coronary and/or vascular disease in line with DLCNS criteria. 9 patients (3.2%) had a personal history of premature cardiovascular disease. The DLCNS was calculated for each patient based on the information available. 225 patients (79.2%) had a score of 3, 36 patients (12.7%) had a score of 4, 12 patients (4.2%) had a score of 5 and 6 patients (2.1%) had a score of 6. This equates to 273 patients (96.1%) with a possible diagnosis of FH, and 6 patients (2.1%) with a probable diagnosis of FH. The mean most recent systolic blood pressure reading for these patients was 128mmHg, and diastolic 76mmHg. 51 patients (18%) were current smokers, 83 (29.2%) were ex-smokers, and 111 (39%) had never smoked. Smoking status was unknown for 38 patients (13.4). 128 patients (45%) were on lipid-lowering treatment at the time of this audit. 60 (21.1%) were on high intensity treatment, 68 (23.9%) were on medium intensity treatment and none were on low intensity treatment. 24.3% of patients were at target LDL. There were 5 patients (1.8%) currently receiving ezetimibe and 1 (0.4%) on fenofibrate. Conclusion A significant number of patients had a LDL >5mmol/l in this audit. Only 45% were on lipid lowering treatment and 24.3% were at a target LDL. This highlights the needs for structured programmes for screening and management of FH in primary care. Acknowledgement/Funding Funded by an unrestricted grant from Amgen

P938Extensive formation of atherosclerotic cardiovascular disease in subjects with severe familial hypercholesterolemia defined by the international atherosclerosis society criteria

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Funabashi ◽  
Y Kataoka ◽  
M Harada-Shiba ◽  
M Hori ◽  
T Doi ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Risk ◽  
Familial Hypercholesterolemia ◽  
Peripheral Artery Disease ◽  
Cardiac Death ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Peripheral Artery ◽  
Lowering Therapy ◽  
Artery Disease

Abstract Introduction The International Atherosclerosis Society (IAS) has proposed “severe familial hypercholesterolemia (FH)” as a FH phenotype with the highest cardiovascular risk. Coronary artery disease (CAD) represents a major atherosclerotic change in FH patients. Given their higher LDL-C level and atherogenic clinical features, more extensive formation of atherosclerosis cardiovascular disease including not only CAD but stroke/peripheral artery disease (PAD) may more frequently occur in severe FH. Methods 481 clinically-diagnosed heterozygous FH subjects were analyzed. Severe FH was defined as untreated LDL-C>10.3 mmol/l, LDL-C>8.0 mmol/l+ 1 high-risk feature, LDL-C>4.9 mmol/l + 2 high-risk features or presence of clinical ASCVD according to IAS proposed statement. Cardiac (cardiac death and ACS) and non-cardiac (stroke and peripheral artery disease) events were compared in severe and non-severe FH subjects. Results Severe FH was identified in 50.1% of study subjects. They exhibit increased levels of LDL-C and Lipoprotein (a) with a higher frequency of LDLR mutation. Furthermore, a proportion of %LDL-C reduction>50% was greater in severe FH under more lipid-lowering therapy (Table). However, during the observational period (median=6.3 years), severe FH was associated with a 5.9-fold (95% CI, 2.05–25.2; p=0.004) and 5.8-fold (95% CI, 2.02–24.7; p=0.004) greater likelihood of experiencing cardiac-death/ACS and stroke/PAD, respectively (picture). Multivariate analysis demonstrated severe FH as an independent predictor of both cardiac-death/ACS (hazard ratio=3.39, 95% CI=1.12–14.7, p=0.02) and stroke/PAD (hazard ratio=3.38, 95% CI=1.16–14.3, p=0.02) events. Clinical characteristics of severe FH Non-severe FH Severe FH P-value Baseline LDL-C (mmol/l) 5.3±1.5 6.6±2.0 <0.0001 Lp(a) (mg/dl) 15 [8–28] 21 [10–49] <0.0001 LDLR mutation (%) 49.6% 58.9% 0.00398 On-treatment LDL-C (mmol) 133 [106–165] 135 [103–169] 0.9856 %LDL-C reduction>50% 21.3% 49.8% <0.0001 High-intensity statin (%) 13.3% 42.3% <0.0001 PCSK9 inhibitor (%) 6.3% 21.2% <0.0001 Clinical outcome Conclusions Severe FH subjects exhibit substantial atherosclerotic risks for coronary, carotid and peripheral arteries despite lipid lowering therapy. Our finding underscore the screening of systemic arteries and the adoption of further stringent lipid management in severe FH patients.

scholarly journals Absolute risk of cardiovascular disease events, and blood pressure‐ and lipid‐lowering therapy in Australia

2016 ◽  
Vol 204 (8) ◽  
pp. 320-320 ◽  
Author(s):  
Emily Banks ◽  
Simon R Crouch ◽  
Rosemary J Korda ◽  
Bill Stavreski ◽  
Karen Page ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Absolute Risk ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy
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