Subject(s)
Hyperlipoproteinemias , Hypolipidemic Agents , Lipoprotein(a) , RNA, Small Interfering , Humans , Lipoprotein(a)/blood , RNA, Small Interfering/adverse effects , RNA, Small Interfering/therapeutic use , Hypolipidemic Agents/adverse effects , Hypolipidemic Agents/therapeutic use , Hyperlipoproteinemias/blood , Hyperlipoproteinemias/drug therapySubject(s)
Blood Component Removal , Cardiovascular Diseases , Lipoprotein(a) , PCSK9 Inhibitors , Humans , Lipoprotein(a)/blood , Blood Component Removal/adverse effects , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/blood , Incidence , Male , Female , Middle Aged , Biomarkers/blood , Treatment Outcome , Serine Proteinase Inhibitors/therapeutic use , Serine Proteinase Inhibitors/adverse effects , Aged , Hyperlipoproteinemias/blood , Hyperlipoproteinemias/therapy , Hyperlipoproteinemias/complications , Hyperlipoproteinemias/epidemiology , Hyperlipoproteinemias/drug therapy , Hyperlipoproteinemias/diagnosis , Proprotein Convertase 9/metabolismSubject(s)
Hyperlipoproteinemias , Hypolipidemic Agents , Lipoprotein(a) , RNA, Small Interfering , Humans , Clinical Trials as Topic , Hyperlipoproteinemias/blood , Hyperlipoproteinemias/drug therapy , Hypolipidemic Agents/adverse effects , Hypolipidemic Agents/therapeutic use , Lipoprotein(a)/blood , RNA, Small Interfering/adverse effects , RNA, Small Interfering/therapeutic useABSTRACT
PURPOSE: Hyperlipoproteinemia (a) is a prevalent complication in dialysis patients, with no valid treatment strategy. The aim of this narrative review was to investigate the clinical significance of hyperlipoproteinemia (a) and phytoestrogen therapy in dialysis patients. METHODS: A comprehensive literature search of the published data was performed regarding the effects of phytoestrogen therapy on hyperlipoproteinemia (a) in dialysis patients. FINDINGS: Hyperlipoproteinemia (a) occurs in dialysis patients due to decreased catabolism and increased synthesis of lipoprotein (a) [Lp(a)]. A few clinical trials have studied the effects of phytoestrogens on serum Lp(a). All studies of dialysis patients or nonuremic individuals with hyperlipoproteinemia (a), except one, showed that phytoestrogens could significantly reduce serum Lp(a) levels. However, all investigations of phytoestrogen therapy in individuals with normal serum Lp(a) levels showed that it had no effect on serum Lp(a). Phytoestrogens seem to have effects similar to those of estrogen in lowering Lp(a) concentrations. IMPLICATIONS: Considering the high prevalence of hyperlipoproteinemia (a) in dialysis patients, phytoestrogen therapy is a reasonable approach for reducing serum Lp(a) levels and its complications in these patients.
Subject(s)
Hyperlipoproteinemias , Phytoestrogens , Humans , Phytoestrogens/therapeutic use , Renal Dialysis/adverse effects , Lipoprotein(a) , Hyperlipoproteinemias/drug therapyABSTRACT
Importance: In patients with coronary artery disease, some guidelines recommend initial statin treatment with high-intensity statins to achieve at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C). An alternative approach is to begin with moderate-intensity statins and titrate to a specific LDL-C goal. These alternatives have not been compared head-to-head in a clinical trial involving patients with known coronary artery disease. Objective: To assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease. Design, Setting, and Participants: A randomized, multicenter, noninferiority trial in patients with a coronary disease diagnosis treated at 12 centers in South Korea (enrollment: September 9, 2016, through November 27, 2019; final follow-up: October 26, 2022). Interventions: Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg. Main Outcomes and Measures: Primary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points. Results: Among 4400 patients, 4341 patients (98.7%) completed the trial (mean [SD] age, 65.1 [9.9] years; 1228 females [27.9%]). In the treat-to-target group (n = 2200), which had 6449 person-years of follow-up, moderate-intensity and high-intensity dosing were used in 43% and 54%, respectively. The mean (SD) LDL-C level for 3 years was 69.1 (17.8) mg/dL in the treat-to-target group and 68.4 (20.1) mg/dL in the high-intensity statin group (n = 2200) (P = .21, compared with the treat-to-target group). The primary end point occurred in 177 patients (8.1%) in the treat-to-target group and 190 patients (8.7%) in the high-intensity statin group (absolute difference, -0.6 percentage points [upper boundary of the 1-sided 97.5% CI, 1.1 percentage points]; P < .001 for noninferiority). Conclusions and Relevance: Among patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02579499.
Subject(s)
Atorvastatin , Cholesterol, LDL , Coronary Artery Disease , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hyperlipoproteinemias , Rosuvastatin Calcium , Aged , Female , Humans , Cholesterol, LDL/blood , Coronary Artery Disease/blood , Coronary Artery Disease/complications , Coronary Artery Disease/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Myocardial Infarction/etiology , Stroke/etiology , Treatment Outcome , Hyperlipoproteinemias/blood , Hyperlipoproteinemias/complications , Hyperlipoproteinemias/drug therapy , Male , Middle Aged , Rosuvastatin Calcium/administration & dosage , Rosuvastatin Calcium/adverse effects , Rosuvastatin Calcium/therapeutic use , Atorvastatin/administration & dosage , Atorvastatin/adverse effects , Atorvastatin/therapeutic useABSTRACT
Chylomicronemia syndrome is a metabolic condition characterized by severe hypertriglyceridemia and fasting chylomicronemia, secondary to an alteration in the ability to metabolize triglycerides. It can respond to different etiologies, the most frequent being multifactorial. Familial chylomicronemia syndrome, on the other hand, represents an infrequent cause of chylomicronemia syndrome, showing an autosomal recessive inheritance pattern. It's caused by pathogenic variants in genes related to chylomicron's metabolism, mainly LPL1 gene. One of the main associated risks is the occurrence of acute pancreatitis, which can also have a recurrent course. The primary therapy goal in patients with this condition is prevention of pancreatitis and related comorbidities. The treatment basis consists in reduce chylomicron formation by restriction of dietary fat, in association with physical activity and pharmacologic therapy. It is important to distinguish the etiology of chylomicronemia syndrome since it has repercussions in terms of response to treatment, complications, and recurrence risk. (AU)
Subject(s)
Humans , Animals , Male , Adult , Middle Aged , Aged , Aged, 80 and over , Hyperlipoproteinemias/genetics , Hyperlipoproteinemias/diagnosis , Hyperlipoproteinemias/drug therapy , Hyperlipoproteinemias/therapy , Hyperlipoproteinemia Type I/geneticsSubject(s)
Aortic Valve Stenosis , Aortic Valve/pathology , Calcinosis , Hyperlipoproteinemias , Lipid Regulating Agents/therapeutic use , Lipoprotein(a) , Aortic Valve Stenosis/blood , Aortic Valve Stenosis/diagnosis , Aortic Valve Stenosis/prevention & control , Calcinosis/blood , Calcinosis/diagnosis , Calcinosis/prevention & control , Disease Progression , Heart Disease Risk Factors , Humans , Hyperlipoproteinemias/blood , Hyperlipoproteinemias/drug therapy , Lipoprotein(a)/blood , Lipoprotein(a)/metabolism , Patient Selection , Secondary Prevention/ethics , Secondary Prevention/methods , Time-to-TreatmentABSTRACT
OBJECTIVES: To investigate the prevalence and quantity of aortic valve calcium (AVC) in two large cohorts, stratified according to age and lipoprotein(a) (Lp(a)), and to assess the association between Lp(a) and AVC. METHODS: We included 2412 participants from the population-based Rotterdam Study (52% women, mean age=69.6±6.3 years) and 859 apparently healthy individuals from the Amsterdam University Medical Centers (UMC) outpatient clinic (57% women, mean age=45.9±11.6 years). All individuals underwent blood sampling to determine Lp(a) concentration and non-enhanced cardiac CT to assess AVC. Logistic and linear regression analyses were performed to investigate the associations of Lp(a) with the presence and amount of AVC. RESULTS: The prevalence of AVC was 33.1% in the Rotterdam Study and 5.4% in the Amsterdam UMC cohort. Higher Lp(a) concentrations were independently associated with presence of AVC in both cohorts (OR per 50 mg/dL increase in Lp(a): 1.54 (95% CI 1.36 to 1.75) in the Rotterdam Study cohort and 2.02 (95% CI 1.19 to 3.44) in the Amsterdam UMC cohort). In the Rotterdam Study cohort, higher Lp(a) concentrations were also associated with increase in aortic valve Agatston score (ß 0.19, 95% CI 0.06 to 0.32 per 50 mg/dL increase). CONCLUSIONS: Lp(a) is robustly associated with presence of AVC in a wide age range of individuals. These results provide further rationale to assess the effect of Lp(a) lowering interventions in individuals with early AVC to prevent end-stage aortic valve stenosis.
Subject(s)
Aortic Valve Stenosis , Aortic Valve/pathology , Calcinosis , Hyperlipoproteinemias , Lipid Regulating Agents/therapeutic use , Lipoprotein(a) , Aged , Aortic Valve/diagnostic imaging , Aortic Valve Stenosis/blood , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/epidemiology , Aortic Valve Stenosis/prevention & control , Calcinosis/blood , Calcinosis/diagnostic imaging , Calcinosis/epidemiology , Calcinosis/prevention & control , Cohort Studies , Correlation of Data , Disease Progression , Female , Heart Disease Risk Factors , Humans , Hyperlipoproteinemias/blood , Hyperlipoproteinemias/drug therapy , Hyperlipoproteinemias/epidemiology , Lipoprotein(a)/blood , Lipoprotein(a)/metabolism , Male , Middle Aged , Multidetector Computed Tomography/methods , Multidetector Computed Tomography/statistics & numerical data , Netherlands/epidemiology , Prevalence , Time-to-TreatmentABSTRACT
Adding to the foundation of statins, ezetimibe and proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i), novel, emerging low-density lipoprotein cholesterol (LDL-C)-lowering therapies are under development for the prevention of cardiovascular disease. Inclisiran, a small interfering RNA molecule that inhibits PCSK9, only needs to be dosed twice a year and has the potential to help overcome current barriers to persistence and adherence to lipid-lowering therapies. Bempedoic acid, which lowers LDL-C upstream from statins, provides a novel alternative for patients with statin intolerance. Angiopoetin-like 3 protein (ANGPTL3) inhibitors have been shown to provide potent LDL-C lowering in patients with homozygous familial hypercholesterolemia without major adverse effects as seen with lomitapide and mipomersen, and may reduce the need for apheresis. Finally, CETP inhibitors may yet be effective with the development of obicetrapib. These novel agents provide the clinician the tools to effectively lower LDL-C across the entire range of LDL-C-induced elevation of cardiovascular risk, from primary prevention and secondary prevention to null-null homozygous familial hypercholesterolemia patients.
Subject(s)
Apolipoproteins B/blood , Cholesterol, LDL/blood , Hypercholesterolemia/drug therapy , Hyperlipoproteinemias/drug therapy , HumansABSTRACT
OBJECTIVE: To study the effects of rutin on serum glucose and lipid levels in hyperglycemic rats. METHODS: Male Wistar rats were subjected to intraperitoneal streptozotocin injections and a high-sugar, high-fat diet to establish a hyperglycemic and hyperlipidemic model. The model was considered to be successfully established in rats with fasting blood sugar (FBS) ≥ 11.1 mmol/L. The study included 6 groups with 10 rats each: a blank control group, a model group, a metformin group, and groups on large, medium and small doses of rutin. The groups received intraperitoneal streptozotocin or normal saline for 21 d. FBS, serum lipids, serum insulin, insulin sensitivity index (ISI), and levels of catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were evaluated in all rats. Pancreatic tissue samples were harvested to observe structural changes in islet cells. RESULTS: Large, medium, and small doses of rutin were associated with significantly reduced FBS (P < 0.05), and increased levels of ISI, CAT, GSH-Px and SOD, as well as decreased MDA (P < 0.05). Rutin administration was also related with reduced total cholesterol, triglycerides and low density lipoprotein chesterol, as well as increased high density lipoprotein chesterol (P < 0.05). Histologic evaluation revealed rutin induced repair of damaged islet cells. CONCLUSION: In diabetic rat models, rutin can significantly reduce FBS and blood lipids, improve anti-oxidant activity, increase insulin sensitivity, and induce repair of damaged islet cells.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hyperlipoproteinemias/drug therapy , Hypoglycemic Agents/administration & dosage , Hypolipidemic Agents/administration & dosage , Rutin/administration & dosage , Animals , Blood Glucose/metabolism , Cholesterol, LDL/blood , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Diet, High-Fat/adverse effects , Glutathione Peroxidase/metabolism , Humans , Hyperlipoproteinemias/genetics , Hyperlipoproteinemias/metabolism , Liver/drug effects , Liver/metabolism , Male , Rats , Rats, Wistar , Superoxide Dismutase/metabolism , Triglycerides/bloodABSTRACT
Population, genetic, and clinical studies demonstrated a causative and continuous, from other plasma lipoproteins independent relationship between elevated plasma lipoprotein (a) [Lp(a)] concentration and the development of cardiovascular disease (CVD), mainly those related to athe-rosclerotic CVD, and calcific aortic stenosis. Currently, a strong international consensus is still lacking regarding the single value which would be commonly used to define hyperlipoproteinemia (a). Its prevalence in the general population is estimated to be in the range of 10%-35% in accordance with the most commonly used threshold levels (>30 or >50 mg/dL). Since elevated Lp(a) can be of special importance in patients with some genetic disorders, as well as in individuals with otherwise controlled major risk factors, the identification and establishment of the proper therapeutic interventions that would lower Lp(a) levels and lead to CVD risk reduction could be very important. The majority of the classical lipid-lowering agents (statins, ezetimibe, and fibrates), as well as nutraceuticals (CoQ10 and garlic), appear to have no significant effect on its plasma levels, whereas for the drugs with the demonstrated Lp(a)-lowering effects (aspirin, niacin, and estrogens), their clinical efficacy in reducing cardiovascular (CV) events has not been unequivocally proven yet. Both Lp(a) apheresis and proprotein convertase subtilisin/kexin type 9 inhibitors can reduce the plasma Lp(a) by approximately 20%-30% on average, in parallel with much larger reduction of low-density lipoprotein cholesterol (up to 70%), what puts us in a difficulty to conclude about the true contribution of lowered Lp(a) to the reduction of CV events. The most recent advancement in the field is the introduction of the novel apolipoprotein (a) [apo(a)] antisense oligonucleotide therapy targeting apo(a), which has already proven itself as being very effective in decreasing plasma Lp(a) (by even >90%), but should be further tested in clinical trials. The aim of this review was to present some of the most important accessible scientific data, as well as dilemmas related to the currently and potentially in the near future more widely available therapeutic options for the management of hyperlipoproteinemia (a).
Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hyperlipoproteinemias/drug therapy , Hypolipidemic Agents/therapeutic use , Cardiovascular Diseases/blood , Cardiovascular Diseases/prevention & control , Humans , Lipoprotein(a)/blood , Risk FactorsABSTRACT
PURPOSE OF REVIEW: To summarize latest clinical studies and to put them into perspectives for clinical relevant subgroups and new therapeutic options. RECENT FINDINGS: Have investigated PCSK9 inhibitors in patients with very high cardiovascular risk and insufficient LDL cholesterol lowering under current maximal tolerated lipid-lowering therapy, patients with statin intolerance, or genetic forms of familiar hypercholesterolemia, and patients on LDL apheresis. Purpose of recent cardiovascular endpoint trials has proven cardiovascular benefit of this new approach. PCSK9 inhibition with fully humanized antibodies has proven to be effective, safe, and well-tolerated in reducing cardiovascular risk by LDL cholesterol lowering. Therefore, research interests are to elucidate additional roles and effects of PCSK9 modulation on inflammation and cellular processes of the atherosclerotic plaque and to develop alternative therapeutic strategies addressing PCSK9 as a proven and therefore promising drug target.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Cardiovascular Diseases/prevention & control , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hyperlipoproteinemias/drug therapy , PCSK9 Inhibitors , Antibodies, Monoclonal, Humanized/adverse effects , Atherosclerosis/drug therapy , Cholesterol, LDL/blood , Endocytosis , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Receptors, LDL/metabolism , Risk FactorsABSTRACT
PURPOSE OF REVIEW: High lipoprotein(a) levels are observationally and causally, from human genetics, associated with increased risk of cardiovascular disease including myocardial infarction and aortic valve stenosis. The European Atherosclerosis Society recommends screening for elevated lipoprotein(a) levels in high-risk patients. Different therapies have been suggested and some are used to treat elevated lipoprotein(a) levels such as niacin, PCSK9 inhibitors, and CETP inhibitors; however, to date, no randomized controlled trial has demonstrated that lowering of lipoprotein(a) leads to lower risk of cardiovascular disease. RECENT FINDINGS: Synthetic oligonucleotides can be used to inactivate genes involved in disease processes. To lower lipoprotein(a), two antisense oligonucleotides have been developed, one targeting apolipoprotein B and one targeting apolipoprotein(a). Mipomersen is an antisense oligonucleotide targeting apolipoprotein B and thereby reducing levels of all apolipoprotein B containing lipoproteins in the circulation. Mipomersen has been shown to lower lipoprotein(a) by 20-50% in phase 3 studies. AKCEA-APO(a)-LRx is the most recent antisense oligonucleotide targeting apolipoprotein(a) and thereby uniquely targeting lipoprotein(a). It has been tested in a phase 2 study and has shown to lower lipoprotein(a) levels by 50-80%. The treatment of elevated lipoprotein(a) levels with the newest antisense oligonucleotides seems promising; however, no improvement in cardiovascular disease risk has yet been shown. However, a phase 3 study of AKCEA-APO(a)-LRx is being planned with cardiovascular disease as outcome, and results are awaited with great anticipation.
Subject(s)
Apoprotein(a)/antagonists & inhibitors , Hyperlipoproteinemias/drug therapy , Oligodeoxyribonucleotides, Antisense/pharmacology , Oligodeoxyribonucleotides, Antisense/therapeutic use , Oligonucleotides/pharmacology , Oligonucleotides/therapeutic use , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Apolipoproteins B/antagonists & inhibitors , Atherosclerosis/prevention & control , Cholesterol Ester Transfer Proteins/antagonists & inhibitors , Humans , PCSK9 Inhibitors , RNA InterferenceSubject(s)
Chemical and Drug Induced Liver Injury/etiology , Hepatitis, Autoimmune/etiology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Rosuvastatin Calcium/adverse effects , Alanine Transaminase/blood , Antibodies, Antinuclear/blood , Aspartate Aminotransferases/blood , Autoantibodies/blood , Autoantibodies/immunology , Chemical and Drug Induced Liver Injury/blood , Chemical and Drug Induced Liver Injury/immunology , Hepatitis, Autoimmune/blood , Hepatitis, Autoimmune/immunology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hyperlipoproteinemias/complications , Hyperlipoproteinemias/drug therapy , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , Muscle, Smooth/immunology , Rosuvastatin Calcium/therapeutic use , gamma-Glutamyltransferase/bloodABSTRACT
PURPOSE OF REVIEW: The aim of this study was to review and assess the evidence for low-density lipoprotein cholesterol (LDL-C) treatment goals as presented in current guidelines for primary and secondary prevention of cardiovascular disease. RECENT FINDINGS: Different sets of guidelines and clinical studies for secondary prevention have centered on lower absolute LDL-C targets [<70 mg/dL (<1.8 mmol/L)], greater percent reductions of LDL-C (≥50%), or more intense treatment to achieve greater reductions in cardiovascular risk. Population-based risk models serve as the basis for statin initiation in primary prevention. Reviews of current population risk models for primary prevention show moderate ability to discriminate [with c-statistics ranging from 0.67 to 0.77 (95% CIs from 0.62 to 0.83) for men and women] with poor calibration and overestimation of risk. Individual clinical trial data are not compelling to support specific LDL-C targets and percent reductions in secondary prevention. Increasing utilization of electronic health records and data analytics will enable the development of individualized treatment goals in both primary and secondary prevention.
Subject(s)
Cardiovascular Diseases/prevention & control , Cholesterol, LDL/blood , Hyperlipoproteinemias/blood , Female , Goals , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hyperlipoproteinemias/drug therapy , Hyperlipoproteinemias/prevention & control , Male , Precision Medicine , Primary Prevention , Risk Factors , Secondary PreventionABSTRACT
BACKGROUND: Lipoprotein(a) [Lp(a)] is generally measured as total mass of the entire particle or as apolipoprotein(a) particle number. OBJECTIVE: The cholesterol content of Lp(a) [Lp(a)-C)] can be estimated by the vertical auto profile (VAP) method. We assessed whether this is an accurate surrogate measurement of Lp(a) mass. METHODS: VAP-Lp(a)-C and VAP-high density lipoprotein cholesterol (HDL-C) estimated by the VAP technique, Lp(a) mass, oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) that primarily reflect OxPL on Lp(a), and HDL-C measured by enzymatic methods were measured in 552 hypercholesterolemic patients at baseline and 24 weeks after therapy with niacin monotherapy (N = 118), ezetimibe/simvastatin monotherapy (n = 155), or ezetimibe/simvastatin (10/20 mg) + niacin (to 2 g) (N = 279) in a randomized, double-blind trial. RESULTS: VAP-Lp(a)-C correlated only modestly with Lp(a) mass at baseline (r = 0.56, P < .001) and 24 weeks (r = 0.56, P < .001), explaining only 31% of the association. VAP-Lp(a)-C correlated with HDL-C at baseline (r = 0.34, P < .001) and 24 weeks (r = 0.30, P < .001) and with VAP-HDL-C at baseline (r = 39, P < .001) and 24 weeks (r = 0.33, P < .001). In contrast, Lp(a) mass did not correlate with HDL-C at baseline (r = 0.06, P = .12) and 24 weeks (r = -0.01 P = .91). Lp(a) mass correlated strongly with oxidized phospholipids on apolipoprotein B-100 at baseline (r = 0.81, P < .001) and 24 weeks (r = 0.79, P < .001). VAP-Lp(a)-C levels increased linearly with HDL-C and VAP-HDL-C quartiles (P < .001 for both) but Lp(a) mass did not. Quantitating the percent of cholesterol present on Lp(a) by dividing VAP-Lp(a)-C by Lp(a) mass revealed that 25% of patients had a percentage >100, which is not possible. CONCLUSIONS: VAP-Lp(a)-C is a poor estimate for Lp(a) mass and likely reflects the content of HDL-C in the overlapping density spectrum of Lp(a) and HDL. These data suggest that patients with prior VAP-Lp(a)-C measurements may have misclassification of Lp(a)-related risk.
Subject(s)
Cholesterol, HDL/blood , Hyperlipoproteinemias/diagnosis , Lipoprotein(a)/blood , Adolescent , Adult , Aged , Anticholesteremic Agents/therapeutic use , Apolipoprotein B-100/blood , Double-Blind Method , Drug Therapy, Combination , Ezetimibe/therapeutic use , Female , Humans , Hyperlipoproteinemias/blood , Hyperlipoproteinemias/drug therapy , Male , Middle Aged , Niacin/therapeutic use , Phospholipids/blood , Phospholipids/chemistry , Simvastatin/therapeutic use , Triglycerides/blood , Young AdultABSTRACT
OBJECTIVE: High lipoprotein(a) (Lp[a]) is the most common genetic dyslipidemia and is a causal factor for myocardial infarction (MI) and aortic stenosis (AS). We sought to estimate the population impact of Lp(a) lowering that could be achieved in primary prevention using the therapies in development. APPROACH AND RESULTS: We used published data from 2 prospective cohorts. High Lp(a) was defined as ≥50 mg/dL (≈20th percentile). Relative risk, attributable risk, the attributable risk percentage, population attributable risk, and the population attributable risk percentage were calculated as measures of the population impact. For MI, the event rate was 4.0% versus 2.8% for high versus low Lp(a) (relative risk, 1.46; 95% confidence interval [CI], 1.45-1.46). The attributable risk was 1.26% (95% CI, 1.24-1.27), corresponding to 31.3% (95% CI, 31.0-31.7) of the excess MI risk in those with high Lp(a). The population attributable risk was 0.21%, representing a population attributable risk percentage of 7.13%. For AS, the event rate was 1.51% versus 0.78% for high versus low Lp(a) (relative risk, 1.95; 95% CI, 1.94-1.97). The attributable risk was 0.74% (95% CI, 0.73-0.75), corresponding to 48.8% (95% CI, 48.3-49.3) of the excess AS risk in those with high Lp(a). The population attributable risk was 0.13%, representing a population attributable risk percentage of 13.9%. In sensitivity analyses targeting the top 10% of Lp(a), the population attributable risk percentage was 5.2% for MI and 7.8% for AS. CONCLUSIONS: Lp(a) lowering among the top 20% of the population distribution for Lp(a) could prevent 1 in 14 cases of MI and 1 in 7 cases of AS, suggesting a major impact on reducing the burden of cardiovascular disease. Targeting the top 10% could prevent 1 in 20 MI cases and 1 in 12 AS cases.
Subject(s)
Aortic Valve Stenosis/prevention & control , Hyperlipoproteinemias/drug therapy , Hypolipidemic Agents/therapeutic use , Lipoprotein(a)/blood , Myocardial Infarction/prevention & control , Aortic Valve Stenosis/diagnosis , Aortic Valve Stenosis/epidemiology , Biomarkers/blood , Denmark/epidemiology , Down-Regulation , Humans , Hyperlipoproteinemias/blood , Hyperlipoproteinemias/diagnosis , Hyperlipoproteinemias/epidemiology , Hypolipidemic Agents/adverse effects , Incidence , Myocardial Infarction/diagnosis , Myocardial Infarction/epidemiology , Prospective Studies , Protective Factors , Risk Assessment , Risk Factors , Time Factors , Treatment OutcomeSubject(s)
Hyperlipoproteinemias/drug therapy , Hypolipidemic Agents/therapeutic use , Lipoprotein(a)/antagonists & inhibitors , Oligonucleotides, Antisense/therapeutic use , Clinical Trials, Phase I as Topic , Clinical Trials, Phase II as Topic , Humans , Hyperlipoproteinemias/blood , Lipoprotein(a)/bloodABSTRACT
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